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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cell. Infect. Microbiol.</journal-id>
<journal-title>Frontiers in Cellular and Infection Microbiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cell. Infect. Microbiol.</abbrev-journal-title>
<issn pub-type="epub">2235-2988</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fcimb.2025.1535246</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cellular and Infection Microbiology</subject>
<subj-group>
<subject>Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Exploring the health benefits of <italic>Ganoderma</italic>: antimicrobial properties and mechanisms of action</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Karunarathna</surname>
<given-names>Samantha C.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/734309/overview"/>
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<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Patabendige</surname>
<given-names>Nimesha M.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Hapuarachchi</surname>
<given-names>Kalani K.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Promputtha</surname>
<given-names>Itthayakorn</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
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<aff id="aff1">
<sup>1</sup>
<institution>Center for Yunnan Plateau Biological Resources Protection and Utilization, College of Biology and Food Engineering, Qujing Normal University</institution>, <addr-line>Qujing, Yunnan</addr-line>,&#xa0;<country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>School of Medical, Molecular and Forensic Sciences, Murdoch University</institution>, <addr-line>Murdoch, WA</addr-line>,&#xa0;<country>Australia</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>College of Biodiversity Conservation, Southwest Forestry University</institution>, <addr-line>Kunming</addr-line>,&#xa0;<country>China</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>Department of Biology, Faculty of Science, Chiang Mai University</institution>, <addr-line>Chiang Mai</addr-line>,&#xa0;<country>Thailand</country>
</aff>
<aff id="aff5">
<sup>5</sup>
<institution>Environmental Science Research Center (ESRC), Chiang Mai University</institution>, <addr-line>Chiang Mai</addr-line>,&#xa0;<country>Thailand</country>
</aff>
<aff id="aff6">
<sup>6</sup>
<institution>Natural Extracts and Innovative Products for Alternative Healthcare Research Group, Faculty of Science, Chiang Mai University</institution>, <addr-line>Chiang Mai</addr-line>,&#xa0;<country>Thailand</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: Blake Billmyre, University of Georgia, United States</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Sabulal Baby, Jawaharlal Nehru Tropical Botanic Garden and Research Institute, India</p>
<p>Prashant R. Desai, University of Wisconsin-Madison, United States</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Itthayakorn Promputtha, <email xlink:href="mailto:itthayakorn.p@cmu.ac.th">itthayakorn.p@cmu.ac.th</email>; Kalani K. Hapuarachchi, <email xlink:href="mailto:kalanifirst@yahoo.com">kalanifirst@yahoo.com</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>18</day>
<month>07</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>15</volume>
<elocation-id>1535246</elocation-id>
<history>
<date date-type="received">
<day>27</day>
<month>11</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>28</day>
<month>05</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2025 Karunarathna, Patabendige, Hapuarachchi and Promputtha</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Karunarathna, Patabendige, Hapuarachchi and Promputtha</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>
<italic>Ganoderma</italic>, a well-known medicinal mushroom, has garnered attention for its broad therapeutic properties, particularly its potent antimicrobial activities. This review focuses on the mechanisms of action and bioactive compounds responsible for the ability of <italic>Ganoderma</italic> to inhibit various pathogenic microorganisms. The polysaccharides, triterpenoids, proteins, and phenolic compounds in <italic>Ganoderma</italic> exhibit strong antimicrobial effects by targeting bacterial cell walls, disrupting membrane integrity, and inhibiting key microbial enzymes. These compounds are effective against a wide range of bacteria, including <italic>Staphylococcus aureus</italic>, <italic>Escherichia coli</italic>, <italic>Pseudomonas aeruginosa</italic>, and various fungi. Triterpenoids, specifically, have demonstrated efficacy in modulating immune responses, further enhancing the body&#x2019;s defense mechanisms against infections. Furthermore, the role of <italic>Ganoderma</italic> in preventing biofilm formation and combating antibiotic-resistant strains highlights its potential as a natural antimicrobial agent. While <italic>in vitro</italic> and <italic>in vivo</italic> studies strongly support the antimicrobial properties of <italic>Ganoderma</italic>, future resety -50arch should focus on large-scale clinical trials to confirm its efficacy and explore its synergistic effects with conventional antibiotics. Establishing standardized dosages and exploring the molecular pathways of its antimicrobial actions will be key to incorporating <italic>Ganoderma</italic> into clinical practice for infection control.</p>
</abstract>
<kwd-group>
<kwd>antimicrobial activity</kwd>
<kwd>biofilm inhibition</kwd>
<kwd>pathogenic bacteria</kwd>
<kwd>polysaccharides</kwd>
<kwd>synergistic effects</kwd>
<kwd>triterpenoids</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="9"/>
<equation-count count="0"/>
<ref-count count="257"/>
<page-count count="26"/>
<word-count count="13547"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Fungal Pathogenesis</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>
<italic>Ganoderma</italic> is a genus of medicinal mushrooms used for thousands of years in traditional East Asian medicine. Revered for its numerous therapeutic benefits, <italic>Ganoderma</italic> has gained significant attention in modern scientific research due to its bioactive compounds exhibiting various pharmacological activities (<xref ref-type="bibr" rid="B108">Karunarathna et&#xa0;al., 2024a</xref>). Among these activities, its antimicrobial properties stand out as an area of growing interest, particularly in an era where antimicrobial resistance (AMR) poses a significant global health threat (<xref ref-type="bibr" rid="B168">Pandey et&#xa0;al., 2020</xref>). Understanding the mechanisms by which <italic>Ganoderma</italic> exerts its antimicrobial effects is critical for developing novel therapies that harness its bioactive compounds to combat various infectious diseases (<xref ref-type="bibr" rid="B147">Mousavi et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B109">Karunarathna et&#xa0;al., 2024b</xref>). The antimicrobial properties of <italic>Ganoderma</italic> are attributed primarily to its rich content of bioactive compounds such as polysaccharides, triterpenoids, phenolic compounds, proteins, and peptides (<xref ref-type="bibr" rid="B5">Ahmad, 2019</xref>; <xref ref-type="bibr" rid="B37">Cadar et&#xa0;al., 2023</xref>). These compounds have been shown to work synergistically to inhibit the growth of various pathogenic microorganisms, including bacteria, fungi, and viruses. Historically, <italic>Ganoderma</italic> has been used in traditional medicine to treat infections, improve immune function, and promote overall health. These traditional uses are being validated by scientific research, which has provided evidence for <italic>Ganoderma</italic>&#x2019;s effectiveness in inhibiting microbial growth and enhancing immune responses to infections.</p>
<p>One of the most studied bioactive compounds in <italic>Ganoderma</italic> is polysaccharides, particularly &#x3b2;-glucans, which are known to modulate immune responses and exhibit strong antimicrobial effects. Polysaccharides have been shown to activate macrophages and other immune cells, enhancing the ability of the body to detect and eliminate microbial pathogens. Triterpenoids, another significant class of compounds in <italic>Ganoderma</italic>, have demonstrated the ability to disrupt microbial cell walls and inhibit the replication of pathogens, particularly bacteria and fungi (<xref ref-type="bibr" rid="B125">Liu et&#xa0;al., 2022</xref>). In addition to these, phenolic compounds and polyketides of farnesyl quonines types and peptides isolated from <italic>Ganoderma</italic> also play crucial roles in its antimicrobial activity by scavenging free radicals, reducing oxidative stress, and enhancing the body&#x2019;s natural defense mechanisms (<xref ref-type="bibr" rid="B28">Basnet et&#xa0;al., 2017</xref>). The antimicrobial properties of <italic>Ganoderma</italic> have been documented in various <italic>in vitro</italic> and <italic>in vivo</italic> studies, which have explored its efficacy against a wide range of pathogens. For instance, <italic>Ganoderma</italic> has potent inhibitory effects on Gram-positive and Gram-negative bacteria, including <italic>Staphylococcus aureus</italic>, <italic>Escherichia coli</italic>, and <italic>Pseudomonas aeruginosa</italic>. Moreover, it has shown antifungal activity against <italic>Candida albicans</italic>, a common cause of fungal infections in immunocompromised individuals (<xref ref-type="bibr" rid="B6">Ahmad et&#xa0;al., 2024</xref>). Furthermore, emerging studies have investigated its potential antiviral activity, with some evidence suggesting that <italic>Ganoderma</italic> extracts may inhibit the replication of viruses such as herpes simplex virus (HSV) and influenza virus (<xref ref-type="bibr" rid="B196">Seo and Choi, 2021</xref>). These findings suggest that <italic>Ganoderma</italic> could be a valuable natural alternative or adjunct to conventional antimicrobial therapies, particularly in the context of rising antibiotic resistance. The mechanisms through which <italic>Ganoderma</italic> exerts its antimicrobial effects are complex and multifaceted. Disruption of microbial cell walls, inhibition of nucleic acid synthesis, and modulation of immune responses are among the primary mechanisms identified in current research. <italic>Ganoderma</italic> bioactive compounds interact with microbial cells, weakening their structural integrity and preventing proliferation. Moreover, <italic>Ganoderma</italic>&#x2019;s ability to modulate the host&#x2019;s immune system enhances its antimicrobial efficacy, as it not only directly inhibits pathogens but also strengthens the body&#x2019;s natural defenses against infections (<xref ref-type="bibr" rid="B81">Gao et&#xa0;al., 2005</xref>). Despite the promising antimicrobial potential of <italic>Ganoderma</italic>, several challenges remain. One major limitation is the variability in the composition of bioactive compounds across different <italic>Ganoderma</italic> species and even within the same species depending on environmental factors and cultivation methods. This variability makes it difficult to standardize extracts for clinical use. In addition, while <italic>in vitro</italic> and animal studies have provided valuable insights, more human clinical trials are needed to confirm the safety and efficacy of <italic>Ganoderma</italic> as an antimicrobial agent. Future research should focus on identifying the compounds responsible for antimicrobial effects of <italic>Ganoderma</italic> and developing standardized formulations for therapeutic use. <italic>Ganoderma</italic> represents a promising natural source of antimicrobial agents with potential applications in treating various infections. Its ability to modulate the immune system and directly inhibit microbial growth makes it an attractive candidate for developing novel antimicrobial therapies. However, further research is necessary to fully understand its mechanisms of action and overcome the challenges associated with its variability and standardization. As antibiotic resistance continues to rise globally, exploring natural alternatives such as <italic>Ganoderma</italic> is becoming increasingly important. This review aims to provide a comprehensive overview of the antimicrobial properties of <italic>Ganoderma</italic>, focusing on recent advances in understanding its bioactive compounds, mechanisms of action, and potential therapeutic applications, particularly in the context of rising AMR. The novelty of this work lies in synthesizing recent findings and highlighting emerging insights into the role of <italic>Ganoderma</italic> as a promising natural antimicrobial agent.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>
<italic>Ganoderma</italic> bioactive compounds</title>
<p>
<italic>Ganoderma</italic> species produce a variety of bioactive compounds with significant health benefits, including polysaccharides, triterpenoids, proteins, peptides, and phenolic compounds, each contributing uniquely to their therapeutic potential. This section provides a brief overview of these compounds, highlighting their structures, functions, and mechanisms of action. Detailed phytochemical and bioactivity profiles of <italic>Ganoderma</italic> have been extensively reviewed (<xref ref-type="bibr" rid="B22">Baby et&#xa0;al., 2015</xref>; <xref ref-type="bibr" rid="B36">Blundell et&#xa0;al., 2023</xref>).</p>
<p>Among the most studied bioactive compounds are the polysaccharides, particularly &#x3b2;-glucans from <italic>G. lucidum</italic>. These complex carbohydrates, characterized by &#x3b2;-D-glucose linkages, are categorized by molecular weight and solubility, factors that influence their biological activities (<xref ref-type="bibr" rid="B108">Karunarathna et&#xa0;al., 2024a</xref>). &#x3b2;-glucans are known to modulate the immune system by activating macrophages and natural killer cells, enhancing the immune response of the host (<xref ref-type="bibr" rid="B49">Chen et&#xa0;al., 2023</xref>). They also impact cellular signaling pathways, regulating cytokine production and inhibiting tumor growth (<xref ref-type="bibr" rid="B252">Zhang et&#xa0;al., 2023</xref>). The structural features of <italic>Ganoderma</italic> polysaccharides, such as branching patterns and molecular configurations, play a critical role in determining their therapeutic efficacy (<xref ref-type="bibr" rid="B244">Wu et&#xa0;al., 2025</xref>).</p>
<p>Triterpenoids, another major class of <italic>Ganoderma</italic> bioactive compounds, include ganoderic and lucidenic acids. These compounds, with their multi-ring structures and diverse functional groups, contribute to a wide range of biological activities (<xref ref-type="bibr" rid="B180">Raza et&#xa0;al., 2024</xref>; <xref ref-type="bibr" rid="B167">Pan et&#xa0;al., 2025</xref>). Triterpenoids have shown potent immunomodulatory effects by modulating cytokine production and enhancing the activity of immune cells like T cells and macrophages (<xref ref-type="bibr" rid="B98">Jin et&#xa0;al., 2025</xref>; <xref ref-type="bibr" rid="B128">Lucius, 2025</xref>). They also demonstrate broad-spectrum antimicrobial activity by disrupting microbial cell membranes and interfering with enzymatic processes critical for pathogen survival (<xref ref-type="bibr" rid="B6">Ahmad et&#xa0;al., 2024</xref>; <xref ref-type="bibr" rid="B238">Wang et&#xa0;al., 2017</xref>; <xref ref-type="bibr" rid="B74">Ewunkem et&#xa0;al., 2024</xref>; <xref ref-type="bibr" rid="B121">Liang et&#xa0;al., 2024</xref>). Phenolic compounds in <italic>Ganoderma</italic>, such as flavonoids, phenolic acids, and polyphenols, are well-known for their antioxidant properties. They reduce oxidative stress by neutralizing free radicals and reactive oxygen species (ROS). Their antioxidant effects are largely due to their electron-donating ability, stabilizing free radicals and preventing cellular damage and inflammation (<xref ref-type="bibr" rid="B112">Kebaili et&#xa0;al., 2021</xref>; <xref ref-type="bibr" rid="B172">Plosca et&#xa0;al., 2025</xref>). In addition to their antioxidative functions, phenolic compounds also exert antimicrobial activity by disrupting microbial cell structures and inhibiting key enzymatic functions necessary for pathogen survival (<xref ref-type="bibr" rid="B179">Ra&#x161;eta et&#xa0;al., 2023</xref>). The multifunctional roles of these compounds underscore their significance in maintaining health and preventing disease.</p>
</sec>
<sec id="s3">
<label>3</label>
<title>Mechanisms of antimicrobial action</title>
<p>
<italic>Ganoderma</italic> species possess many bioactive compounds that exhibit significant antimicrobial activities. The mechanisms by which these compounds act against pathogens are multifaceted, involving direct effects on microbial structures and functions and modulation of the host immune system (<xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>).</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Potential antimicrobial properties of <italic>Ganoderma</italic> (<xref ref-type="bibr" rid="B6">Ahmad et&#xa0;al., 2024</xref>).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fcimb-15-1535246-g001.tif"/>
</fig>
<sec id="s3_1">
<label>3.1</label>
<title>Disruption of microbial cell walls</title>
<p>One of the primary antimicrobial mechanisms of <italic>Ganoderma</italic> bioactive compounds is the disruption of microbial cell walls. Triterpenoids, such as ganoderic acids found in <italic>Ganoderma lucidum</italic>, interact with the lipid components of bacterial and fungal cell membranes, leading to increased permeability and cell lysis. This disruption compromises the integrity of the microbial cell wall, causing leakage of cellular contents and, ultimately, cell death (<xref ref-type="bibr" rid="B74">Ewunkem et&#xa0;al., 2024</xref>; <xref ref-type="bibr" rid="B165">Ojha, 2025</xref>).</p>
</sec>
<sec id="s3_2">
<label>3.2</label>
<title>Inhibition of nucleic acid synthesis</title>
<p>
<italic>Ganoderma</italic> bioactive compounds also inhibit microbial proliferation by interfering with nucleic acid synthesis. Polysaccharides extracted from <italic>Ganoderma</italic> species have been reported to inhibit DNA and RNA synthesis in pathogenic microbes. They achieve this by binding to nucleic acids or key enzymes involved in replication and transcription processes, thereby hindering microbial growth and replication. This inhibition of genetic material synthesis is crucial in preventing the spread and survival of the pathogen (<xref ref-type="bibr" rid="B229">Su&#x142;kowska-Ziaja et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B121">Liang et&#xa0;al., 2024</xref>).</p>
</sec>
<sec id="s3_3">
<label>3.3</label>
<title>Immune modulation</title>
<p>
<italic>Ganoderma</italic> compounds enhance the immune response of the body, providing an indirect mechanism to combat infections. Polysaccharides, especially beta-glucans, are known to modulate the immune system by activating macrophages, dendritic cells, and natural killer cells (<xref ref-type="bibr" rid="B252">Zhang et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B254">Zhong et&#xa0;al., 2024</xref>). This activation increases cytokine and antibody production, bolstering the body&#x2019;s ability to fight microbial invaders. The immunomodulatory effects of <italic>Ganoderma</italic> not only enhance the innate immune response but also promote adaptive immunity. By stimulating immune cell proliferation and differentiation, these compounds help establish long-term immunity against specific pathogens (<xref ref-type="bibr" rid="B198">Seweryn et&#xa0;al., 2021</xref>; <xref ref-type="bibr" rid="B255">Zhong et&#xa0;al., 2023</xref>). This dual action makes <italic>Ganoderma</italic> an effective agent in preventing and managing infections.</p>
</sec>
<sec id="s3_4">
<label>3.4</label>
<title>Oxidative stress regulation</title>
<p>Oxidative stress plays a significant role in the pathogenesis of many microbial infections. Phenolic compounds of <italic>Ganoderma</italic> exhibit strong antioxidant properties, which help balance ROS within microbial cells (<xref ref-type="bibr" rid="B247">Zahmoul et&#xa0;al., 2024</xref>; <xref ref-type="bibr" rid="B172">Plosca et&#xa0;al., 2025</xref>). By inducing oxidative stress beyond the tolerance levels of microbes, these compounds can lead to cellular damage and death of the pathogens. Conversely, in host cells, <italic>Ganoderma</italic> antioxidants protect against oxidative damage caused by infections. They scavenge excess ROS, reducing inflammation and preventing tissue damage (<xref ref-type="bibr" rid="B6">Ahmad et&#xa0;al., 2024</xref>; <xref ref-type="bibr" rid="B47">Chen et&#xa0;al., 2024</xref>). This protective effect supports the healing process and restores normal cellular functions.</p>
</sec>
</sec>
<sec id="s4">
<label>4</label>
<title>Synergistic effects of compounds</title>
<p>The antimicrobial efficacy of <italic>Ganoderma</italic> species, particularly <italic>G. lucidum</italic>, is not solely attributed to individual bioactive compounds. Instead, the interactions between various compounds&#x2014;such as polysaccharides, triterpenoids, proteins, peptides, and phenolic compounds&#x2014;create synergistic effects that significantly enhance their therapeutic potential. Synergy refers to the increased effectiveness when these compounds work together, often producing results greater than the sum of their actions.</p>
<sec id="s4_1">
<label>4.1</label>
<title>Interaction between different bioactive compounds</title>
<p>Polysaccharides and triterpenoids are two of the most studied bioactive compounds in <italic>Ganoderma</italic>. Polysaccharides are known for their immunomodulatory properties, while triterpenoids have potent antimicrobial and anti-inflammatory activities. Combined, these two compounds demonstrate enhanced immunomodulatory effects, stimulating the body&#x2019;s immune system to fight off infections more effectively (<xref ref-type="bibr" rid="B81">Gao et&#xa0;al., 2005</xref>). For example, while triterpenoids may directly disrupt microbial cell membranes, polysaccharides boost the production of immune cells like macrophages and natural killer (NK) cells, leading to a synergistic antimicrobial action (<xref ref-type="bibr" rid="B198">Seweryn et&#xa0;al., 2021</xref>; <xref ref-type="bibr" rid="B255">Zhong et&#xa0;al., 2023</xref>).</p>
<sec id="s4_1_1">
<label>4.1.1</label>
<title>Proteins and peptides with triterpenoids</title>
<p>Proteins and peptides in <italic>Ganoderma</italic> also exhibit antimicrobial properties, particularly against bacteria and fungi. When these are used with triterpenoids, the compounds together demonstrate enhanced efficacy. The peptides may disrupt microbial membranes, while triterpenoids inhibit nucleic acid synthesis, thereby preventing microbial replication. This dual mechanism increases the effectiveness of the antimicrobial response, especially in pathogens resistant to single-compound treatments (<xref ref-type="bibr" rid="B55">C&#xf6;r Andrej&#x10d; et&#xa0;al., 2022</xref>; <xref ref-type="bibr" rid="B37">Cadar et&#xa0;al., 2023</xref>).</p>
</sec>
<sec id="s4_1_2">
<label>4.1.2</label>
<title>Phenolic compounds and polysaccharides</title>
<p>Phenolic compounds in <italic>Ganoderma</italic> contribute significantly to its antioxidant activity, reducing oxidative stress within cells. When combined with polysaccharides, these phenolic compounds enhance the immune response and improve the organism&#x2019;s overall resistance to microbial infections. The phenolic compounds neutralize ROS, while polysaccharides improve immune cell signaling. This combination leads to a more efficient and sustained immune response to pathogens, particularly in cases of chronic infections (<xref ref-type="bibr" rid="B198">Seweryn et&#xa0;al., 2021</xref>; <xref ref-type="bibr" rid="B47">Chen et&#xa0;al., 2024</xref>).</p>
</sec>
</sec>
<sec id="s4_2">
<label>4.2</label>
<title>Enhanced antimicrobial activity</title>
<p>Research shows that combining polysaccharides and triterpenoids from <italic>Ganoderma</italic> results in enhanced antibacterial activity. For example, studies on <italic>E. coli</italic> and <italic>S. aureus</italic> have shown that combining these two compounds leads to stronger inhibition of bacterial growth compared to their individual effects. The synergy is observed in the disruption of bacterial cell walls by triterpenoids and the enhancement of immune responses by polysaccharides, which work together to eliminate bacterial infections more efficiently (<xref ref-type="bibr" rid="B6">Ahmad et&#xa0;al., 2024</xref>).</p>
<sec id="s4_2_1">
<label>4.2.1</label>
<title>Synergistic effects against fungal infections</title>
<p>In the case of fungal infections, particularly <italic>C. albicans</italic>, combining polysaccharides with phenolic compounds has been shown to enhance antifungal activity. This combination disrupts fungal cell walls while simultaneously inducing oxidative stress within the fungal cells. The phenolic compounds reduce ROS accumulation, which damages fungal cells, and the polysaccharides enhance the immune response, creating a powerful antifungal effect. The result is a more effective inhibition of <italic>C. albicans</italic> growth and biofilm formation, critical for fungal survival and virulence (<xref ref-type="bibr" rid="B186">Roychoudhury et&#xa0;al., 2024</xref>).</p>
</sec>
<sec id="s4_2_2">
<label>4.2.2</label>
<title>Viral infections</title>
<p>Emerging research also suggests that the synergistic effects of polysaccharides and triterpenoids in <italic>Ganoderma</italic> may extend to viral infections. For instance, in studies on the HSV, a combination of these compounds has demonstrated the ability to inhibit viral replication more effectively than when either compound is used alone. Polysaccharides stimulate immune responses, such as activating macrophages and NK cells, while triterpenoids interfere with viral entry into host cells, resulting in enhanced antiviral activity (<xref ref-type="bibr" rid="B68">Eo et&#xa0;al., 2000</xref>; <xref ref-type="bibr" rid="B30">Bharadwaj et&#xa0;al., 2019</xref>).</p>
</sec>
</sec>
</sec>
<sec id="s5">
<label>5</label>
<title>Research on specific microorganisms</title>
<p>
<italic>Ganoderma</italic> species, particularly <italic>G. lucidum</italic>, have gained recognition for their potent antimicrobial properties against various pathogens. The bioactive compounds in <italic>Ganoderma</italic> exhibit broad-spectrum activity against bacteria, fungi, and viruses, making it a promising natural remedy in combating infections. Below is a detailed review of research focusing on the effects of <italic>Ganoderma</italic> on specific microorganisms. GTs are the most common antimicrobial and antiparasitic compounds reported from <italic>Ganoderma</italic> sp. Farnesyl quinone, a polyketide type, is the second most common antimicrobial and antiparasitic compound from <italic>Ganoderma</italic> sp. Quinones are known to be oxidized derivatives of aromatic compounds and are often readily made from reactive aromatic compounds with electron-donating substituents such as catechols and phenols. Besides GTs, polypeptides, small peptides such as ganodermin, polysaccharides such as sacchachitin, and chitosan also possess antimicrobial and antiparasitic properties (<xref ref-type="bibr" rid="B146">Mothana et&#xa0;al., 2000</xref>; <xref ref-type="bibr" rid="B236">Wang and Ng, 2006</xref>; <xref ref-type="bibr" rid="B191">Sanodiya et&#xa0;al., 2009</xref>; <xref ref-type="bibr" rid="B51">Chuang et&#xa0;al., 2013</xref>). Extracts from fruiting bodies, both wild and cultivated, and mycelia from fermentation broth are used for the isolation of antimicrobial and antiparasitic bioactive compounds. Literature divulges that, most commonly, ethanol (EtoAc) is used to prepare crude extract; sometimes, some researchers prefer other solvents such as chloroform (CHCl<sub>3</sub>), EtOH, and acetone (<xref ref-type="bibr" rid="B94">Isaka et&#xa0;al., 2016</xref>). In addition, our review reveals that hexane and ether are poorly used for the preparation of extract from <italic>Ganoderma</italic> sp. Moreover, some techniques such as microwave, ultrasound, and enzyme treatments can facilitate the breakdown of the cell wall (<xref ref-type="bibr" rid="B76">Ferreira et&#xa0;al., 2015</xref>). Solvents like MeOH, EtOH, CH<sub>2</sub>Cl<sub>2</sub>, CHCl<sub>3</sub>, and aqueous&#x2014;both cold and hot&#x2014;are used for further purification and isolation. Techniques such as thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and column chromatography (CC) are used to facilitate the purification and isolation process (<xref ref-type="bibr" rid="B93">Huie and Di, 2004</xref>).</p>
<sec id="s5_1">
<label>5.1</label>
<title>Bacterial infections</title>
<p>Several studies have demonstrated the efficacy of <italic>Ganoderma</italic> bioactive compounds against pathogenic bacteria, including both Gram-positive and Gram-negative strains. Key compounds, such as triterpenoids, polysaccharides, and peptides, have shown significant antibacterial effects (<xref ref-type="fig" rid="f2">
<bold>Figure 2</bold>
</xref>). <italic>Ganoderma</italic> has been reported as an important source of antimicrobial bioactive compounds. Terpenes, terpenoids, and polyketides of farnesyl quonine types are the major secondary metabolites produced by <italic>Ganoderma</italic> sp. In <italic>Ganoderma</italic> species, more than 316 terpenes have been reported, with the majority of compounds from <italic>G. lucidum</italic> (<xref ref-type="bibr" rid="B245">Xia et&#xa0;al., 2014</xref>).</p>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>Structures of bioactive compounds from <italic>Ganoderma</italic> species with antimicrobial and antiparasitic effects (<xref ref-type="bibr" rid="B28">Basnet et&#xa0;al., 2017</xref>).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fcimb-15-1535246-g002.tif"/>
</fig>
<sec id="s5_1_1">
<label>5.1.1</label>
<title>
<italic>Ganoderma</italic> extracts and fermentation broths</title>
<p>The methanol extract of <italic>G. lucidum</italic> showed antibacterial activity against <italic>E. coli</italic>, <italic>Salmonella typhimurium</italic>, and <italic>Bacillus subtilis</italic> [minimum inhibitory concentration (MIC): 1 mg/well], with bioactive polyphenols, flavonoids, quinones, and terpenes identified (<xref ref-type="bibr" rid="B206">Sheena et&#xa0;al., 2003</xref>). Among 23 Yemeni Basidiomycetes, <italic>Agaricus</italic> sp., <italic>Coriolopsis caperata</italic>, <italic>Ganoderma colossus</italic>, <italic>Ganoderma resinaceum</italic>, <italic>Phellorinia herculea</italic>, and <italic>Tulostoma obesum</italic> exhibited potent antibacterial effects, while <italic>G. resinaceum</italic>, <italic>Inonotus ochroporus</italic>, <italic>Phellinus rimosus</italic>, and <italic>P. herculea</italic> displayed strong antioxidant activity (<xref ref-type="bibr" rid="B9">Al-Fatimi et&#xa0;al., 2005</xref>). <italic>G. lucidum</italic> butanol extracts inhibited microbial growth and disrupted fungal spore formation, suggesting potential for antimicrobial tea formulations (<xref ref-type="bibr" rid="B185">Rofuli et&#xa0;al., 2005</xref>). <italic>Ganoderma applanatum</italic>, <italic>Tricholoma crassum</italic>, and <italic>Trametes corrugata</italic> showed peak antibacterial activity (terpenoids and polysaccharides) after 16 days of fermentation (<xref ref-type="bibr" rid="B33">Bhattacharyya et&#xa0;al., 2006</xref>). <italic>Ganoderma</italic> spp. (e.g., <italic>G. carnosum</italic>) exhibited static, heat-stable effects against pathogens like <italic>E. coli</italic> and <italic>C. albicans</italic> (<xref ref-type="bibr" rid="B246">Yamac and Bilgili, 2006</xref>). Furthermore, chitosan from <italic>Ganoderma tsugae</italic> outperformed doxycycline against <italic>Actinobacillus actinomycetemcomitans</italic>, retaining 56.58% activity after 18 days, highlighting dental applications (<xref ref-type="bibr" rid="B46">Chen et&#xa0;al., 2007</xref>). <italic>G. lucidum</italic> aqueous extracts (from <italic>Persia americana</italic> logs) showed stronger antibacterial effects than methanol extracts (<xref ref-type="bibr" rid="B161">Ofodile and Bikomo, 2008</xref>), while its chloroform extracts inhibited Gram-positive and Gram-negative bacteria via sterols and triterpenoid acids (<xref ref-type="bibr" rid="B113">Keypour et&#xa0;al., 2008</xref>). In addition, <italic>G. applanatum</italic> methanol extracts (rich in palmitic acid) selectively inhibited Gram-negative bacteria (<xref ref-type="bibr" rid="B144">Moradali et&#xa0;al., 2008</xref>).</p>
<p>
<italic>G. applanatum</italic> exhibited antimicrobial activity against <italic>E. coli</italic>, <italic>S. aureus</italic>, <italic>C. albicans</italic>, <italic>Mycobacterium smegmatis</italic>, and <italic>Sporothrix schenckii</italic>, highlighting its therapeutic potential (<xref ref-type="bibr" rid="B27">Barranco et&#xa0;al., 2010</xref>). <italic>G. lucidum</italic> methanol, ethanol, and aqueous extracts showed potent activity against pathogens like <italic>Listeria monocytogenes</italic> and methicillin-resistant <italic>S. aureus</italic> (MRSA), with methanol being the most effective solvent (<xref ref-type="bibr" rid="B16">Aneeshia and Sornaraj, 2010</xref>). <italic>G. applanatum</italic> methanol extract displayed strong DPPH scavenging (82.80%), while <italic>G. lucidum</italic> chloroform extract had notable antioxidant and antibacterial effects, linked to high phenol content (<xref ref-type="bibr" rid="B107">Karaman et&#xa0;al., 2010</xref>). <italic>G. lucidum</italic> inhibited spore germination of <italic>Alternaria brassicicola</italic>, suggesting its potential as a biocontrol agent (<xref ref-type="bibr" rid="B48">Chen and Huang, 2010</xref>). Methanol, acetone, chloroform, and aqueous extracts of <italic>G. lucidum</italic> mycelia inhibited Gram-positive and Gram-negative bacteria (100 mg/mL), with Gram-positive strains more susceptible (<xref ref-type="bibr" rid="B102">Kamble et&#xa0;al., 2011</xref>). Furthermore, in Pakistan, Lahore isolates of <italic>G. lucidum</italic> (G-1, G-3, and G-5) inhibited <italic>Xanthomonas</italic> spp., while G-2 and G-4 were effective against <italic>E. coli</italic> and <italic>Pseudomonas</italic> spp., respectively (<xref ref-type="bibr" rid="B150">Nasim and Ali, 2011</xref>). <italic>G. lucidum</italic> aqueous extract (200 mg) showed a 31-mm inhibition zone against <italic>S. typhi</italic> and <italic>S. aureus</italic>, while its methanolic extract was most antifungal (30 mm against <italic>Mucor indicus</italic>) (<xref ref-type="bibr" rid="B195">Sekaran et&#xa0;al., 2011</xref>). Ethyl acetate extracts of <italic>Ganoderma praelongum</italic> sesquiterpenoids were highly active against MRSA (MIC: 0.390&#x2013;6.25 mg/mL), unlike ineffective polysaccharides (<xref ref-type="bibr" rid="B15">Ameri et&#xa0;al., 2011</xref>). <italic>Ganoderma carnosum</italic> dichloromethane extracts strongly inhibited <italic>S. aureus</italic> and <italic>Micrococcus luteus</italic> (<xref ref-type="bibr" rid="B223">Srivastava and Sharma, 2011</xref>). <italic>Ganoderma formosanum</italic> polysaccharides (d-mannose, d-galactose, and d-glucose) enhanced macrophage activity (TNF-&#x3b1;, nitric oxide, and phagocytosis) and protected mice against <italic>L. monocytogenes</italic> (<xref ref-type="bibr" rid="B237">Wang et&#xa0;al., 2011</xref>).</p>
<p>
<italic>G. lucidum</italic> ethyl acetate extracts showed the strongest antibacterial activity (containing carbohydrates, saponins, and terpenoids), being most effective against <italic>Corynebacterium pyogenes</italic>, <italic>B. subtilis</italic>, and <italic>Klebsiella pneumoniae</italic> though less potent than Ampiclox<sup>R</sup> (<xref ref-type="bibr" rid="B201">Shamaki et&#xa0;al., 2012</xref>). Water extracts inhibited <italic>P. aeruginosa</italic>, <italic>Proteus vulgaris</italic>, and <italic>Enterococcus faecalis</italic> but not <italic>L. monocytogenes</italic>, while hexane/dichloromethane/ethyl acetate showed limited antimicrobial isolation potential (<xref ref-type="bibr" rid="B103">Kamra and Bhatt, 2012</xref>). In Central India, <italic>G. lucidum</italic> aqueous extracts enhanced synthetic antibiotics against <italic>S. aureus</italic>, <italic>K. pneumoniae</italic>, <italic>Bacillus cereus</italic>, and <italic>P. aeruginosa</italic> (<xref ref-type="bibr" rid="B110">Karwa and Rai, 2012</xref>). Acetone extracts showed the strongest activity against <italic>P. aeruginosa</italic> (33 mm zone) and the weakest against <italic>S. aureus/K. pneumoniae</italic> (7 mm), with MICs of 4&#x2013;35 mg/mL (<xref ref-type="bibr" rid="B134">Mehta and Jandaik, 2012</xref>). <italic>G. lucidum</italic> spore and <italic>G. applanatum</italic> polysaccharides inhibited <italic>S. aureus</italic>, <italic>B. cereus</italic>, and <italic>Salmonella enteritidis</italic>, suggesting potential as food supplements (<xref ref-type="bibr" rid="B116">Klaus et&#xa0;al., 2012</xref>). Comparative studies showed that <italic>G. lucidum</italic> had the largest inhibition zones against <italic>E. coli/Klebsiella</italic> sp., though less than standard antibiotics (<xref ref-type="bibr" rid="B117">Krishnaveni and Manikandan, 2014</xref>). Solvent choice significantly impacted activity: benzene extracts best inhibited <italic>E. coli/Neisseria meningitidis</italic> (<xref ref-type="bibr" rid="B210">Shikongo, 2012</xref>), while methanol extracts surpassed ampicillin/streptomycin against <italic>S. aureus/B. cereus</italic> (MIC: 0.0125&#x2013;0.75 mg/mL) (<xref ref-type="bibr" rid="B89">Heleno et&#xa0;al., 2013</xref>). Diethyl ether/chloroform extracts showed strong antagonistic effects (<xref ref-type="bibr" rid="B159">Nithya et&#xa0;al., 2013</xref>). Traditional Namibian uses were validated as <italic>Ganoderma</italic> spp. showed potent Gram-positive/negative activity (<xref ref-type="bibr" rid="B211">Shikongo et&#xa0;al., 2013</xref>). The anti-<italic>S. aureus</italic> activity of <italic>G. applanatum</italic> was linked to soluble saponins/phenols (<xref ref-type="bibr" rid="B149">Nagaraj et&#xa0;al., 2013</xref>). <italic>G. lucidum</italic>, <italic>Pleurotus</italic> spp., and <italic>Agaricus bisporus</italic> demonstrated broad therapeutic potential (<xref ref-type="bibr" rid="B142">Mondal, 2013</xref>).</p>
<p>
<italic>G. lucidum</italic> extracts showed significant antimicrobial activity against <italic>P. aeruginosa</italic>, <italic>E. coli</italic>, <italic>S. aureus</italic>, <italic>Proteus mirabilis</italic>, and <italic>K. pneumoniae</italic>. Aqueous extracts produced 11.0- to 14.0-mm inhibition zones, with bioactive tannins, phenolics, flavonoids, and saponins identified (<xref ref-type="bibr" rid="B75">Fakoya et&#xa0;al., 2013</xref>). HPTLC analysis revealed six flavonoids and four phenolics, with methanol extracts most effective against <italic>K. pneumoniae</italic> (24 &#xb1; 0.666 mm), while Gram-negative bacteria showed greater susceptibility than Gram-positive <italic>S. aureus</italic> (<xref ref-type="bibr" rid="B187">Sakthivigneswari and Dharmaraj, 2013</xref>). <italic>G. praelongum</italic> (0.3%) combined with <italic>Glycyrrhiza glabra</italic> (2.5%) in topical gels significantly inhibited MRSA and enhanced wound healing (<xref ref-type="bibr" rid="B14">Ameri et&#xa0;al., 2013</xref>). <italic>G. tsugae</italic> methanol extracts were most active against <italic>E. coli</italic> (20 &#xb1; 0.577 mm), with Gram-negatives more susceptible than Gram-positives (<xref ref-type="bibr" rid="B80">Ganesan and Dharmaraj, 2013</xref>). <italic>G. applanatum</italic> showed particular efficacy against Gram-positive bacteria (<xref ref-type="bibr" rid="B174">Pushpa et&#xa0;al., 2013</xref>). <italic>G. lucidum</italic> ethanol extracts inhibited <italic>Helicobacter pylori</italic> (MIC &lt; 3 mg/mL) and <italic>S. aureus</italic> (MIC 10 mg/mL) but not <italic>E. coli</italic> (<xref ref-type="bibr" rid="B202">Shang et&#xa0;al., 2013</xref>). <italic>G. lucidum</italic> methanol extracts were active against <italic>E. coli</italic>, <italic>S. aureus</italic>, <italic>B. cereus</italic>, <italic>Enterobacter aerogenes</italic>, and <italic>P. aeruginosa</italic> (<xref ref-type="bibr" rid="B13">Alves et&#xa0;al., 2013</xref>).</p>
<p>Recent studies have demonstrated significant antimicrobial potential in various <italic>Ganoderma</italic> species. <italic>Ganoderma boninense</italic> methanol extracts exhibited strong activity against foodborne pathogens <italic>E. coli</italic> and <italic>S. aureus</italic>, with GC-MS analysis identifying dodecanoic acid and octadecanoic acid as key bioactive compounds (<xref ref-type="bibr" rid="B97">Ismail et&#xa0;al., 2014</xref>). Comparative research on <italic>G. lucidum</italic> strains revealed distinct bioactive profiles, with Serbian specimens showing higher sugar content and anticancer properties, while Chinese varieties contained more organic acids and demonstrated superior antioxidant capacity&#x2014;both strains displayed antimicrobial effects that occasionally surpassed standard drugs (<xref ref-type="bibr" rid="B225">Stojkovi&#x107; et&#xa0;al., 2014</xref>). The extraction method significantly influenced activity, as <italic>G. lucidum</italic> methanolic extracts (500 &#xb5;g/disc) produced the largest inhibition zones (13.04 mm) against <italic>S. aureus</italic> and <italic>P. aeruginosa</italic> (<xref ref-type="bibr" rid="B61">Djide et&#xa0;al., 2014</xref>). Chloroform extracts showed notable efficacy against <italic>S. typhi</italic> (18 mm) and <italic>C. albicans</italic> (17 mm), with analytical techniques confirming triterpenoids and polysaccharides as active components (<xref ref-type="bibr" rid="B85">Gowrie et&#xa0;al., 2014</xref>). Optimized fermentation protocols yielded extracts with antioxidant activity exceeding ascorbic acid and antimicrobial effects against <italic>Shigella dysenteriae</italic>, <italic>E. faecalis</italic>, and <italic>K. pneumoniae</italic> (<xref ref-type="bibr" rid="B166">Paliya et&#xa0;al., 2014</xref>). Additional studies confirmed variable but promising activity of <italic>G. lucidum</italic> against <italic>P. aeruginosa</italic>, <italic>E. coli</italic>, <italic>E. faecalis</italic>, <italic>S. aureus</italic>, and <italic>C. albicans</italic>, with ethanol and chloroform extracts proving most effective (<xref ref-type="bibr" rid="B19">Avc&#x131; et&#xa0;al., 2014</xref>).</p>
<p>Comparative studies of mushroom species revealed that <italic>G. tsugae</italic> had the highest dry weight (16.1 g/100 g), while <italic>A. bisporus</italic> contained superior protein (32.0 mg/g) and glucose (13.2 mg/g) content. <italic>A. bisporus</italic> acetone extracts showed antimicrobial activity against <italic>E. coli</italic> (13 mm) and <italic>P. aeruginosa</italic> (14 mm), whereas <italic>G. tsugae</italic> displayed stronger antibacterial effects in DMSO extracts (<xref ref-type="bibr" rid="B60">Dharmaraj et&#xa0;al., 2014</xref>). Nigerian studies of <italic>G. lucidum</italic> ethanolic extracts identified steroids, triterpenoids, and glycosides with activity against <italic>E. coli</italic> (12 mm), <italic>K. pneumoniae</italic> (12 mm), <italic>P. mirabilis</italic> (13 mm), and <italic>Streptococcus</italic> spp. (14 mm) at 1,000 mg/mL (<xref ref-type="bibr" rid="B73">Etim et&#xa0;al., 2014</xref>). <italic>Ganoderma</italic> sp. DKR1 contained saponins, tannins, and terpenoids, with ethyl acetate extracts active against <italic>Micrococcus</italic> sp., <italic>S. aureus</italic>, and <italic>Salmonella</italic> sp., while chloroform extracts inhibited <italic>E. faecalis</italic> and <italic>Candida</italic> sp (<xref ref-type="bibr" rid="B178">Rajesh and Dhanasekaran, 2014</xref>). <italic>G. lucidum</italic> acetone extracts (50 &#xb5;g/mL) showed potent antibacterial activity (31.60 &#xb1; 0.10 mm) against six bacterial species and antifungal effects at 1,000 mg/mL (<xref ref-type="bibr" rid="B214">Singh et&#xa0;al., 2014</xref>). With rising drug resistance, <italic>G. lucidum</italic> methanolic extracts containing carbohydrates, triterpenoids, and phenolics demonstrated strong antibacterial effects (<xref ref-type="bibr" rid="B199">Shah et&#xa0;al., 2014</xref>). <italic>G. lucidum</italic> spore powder inhibited <italic>Prevotella intermedia</italic> (MIC 3.62 mcg/mL) in 65% of periodontal samples (<xref ref-type="bibr" rid="B152">Nayak et&#xa0;al., 2015</xref>). <italic>Ganoderma australe</italic> exhibited antimicrobial and antioxidant activity from alkaloids, while <italic>G. applanatum</italic> and <italic>Flammulina velutipes</italic> showed medium-dependent effects enhanced by wine yeast (<xref ref-type="bibr" rid="B122">Liew et&#xa0;al., 2015</xref>; <xref ref-type="bibr" rid="B77">Fidler et&#xa0;al., 2015</xref>). <italic>Ganoderma</italic> mycelium extracts outperformed fruiting bodies with lower MIC values against pathogens (<xref ref-type="bibr" rid="B204">Sharma et&#xa0;al., 2015</xref>). <italic>G. lucidum</italic>-enriched soap demonstrated antibacterial activity against <italic>S. aureus</italic> and antioxidant capacity (IC<sub>50</sub> 1.53 mg/mL) (<xref ref-type="bibr" rid="B87">Hayati et&#xa0;al., 2020</xref>). <italic>G. resinaceum</italic> methanol extracts showed significant antioxidant and antimicrobial potential (<xref ref-type="bibr" rid="B248">Zengin et&#xa0;al., 2015</xref>), corroborated by other studies (<xref ref-type="bibr" rid="B92">Hoque et&#xa0;al., 2015</xref>; <xref ref-type="bibr" rid="B115">Kirar et&#xa0;al., 2015</xref>). <italic>G. applanatum</italic> methanolic extracts inhibited <italic>S. typhi</italic> (3.21 mm ZOI) and <italic>P. mirabilis</italic> (3.02 mm ZOI), containing phenolics (20.81 mg/100 g) and flavonoids (23.89 mg/100 g), with nutritional analysis revealing 222.08 Kcal/100 g and 42.72% carbohydrates (<xref ref-type="bibr" rid="B57">Dandapat et&#xa0;al., 2016</xref>).</p>
<p>Recent studies have demonstrated significant antimicrobial and antioxidant properties in various <italic>Ganoderma</italic> species. <italic>G. lucidum</italic> showed strongest inhibition against <italic>Candida glabrata</italic> (25 &#xb1; 1 mm) compared to <italic>C. albicans</italic> and <italic>B. subtilis</italic> (10 &#xb1; 1 mm), with its methanolic extract exhibiting exceptional DPPH radical scavenging activity (IC<sub>50</sub> = 3.82 &#xb1; 0.04 &#x3bc;g/mL) attributed to phenolic compounds (<xref ref-type="bibr" rid="B41">Cel&#x131;k et&#xa0;al., 2014</xref>). Ethanol mycelial extracts of <italic>Ganoderma</italic> species, particularly <italic>G. lucidum</italic> BEOFB 433, displayed both antibacterial effects and antifungal activity against <italic>Aspergillus glaucus</italic> and <italic>Trichoderma viride</italic> (<xref ref-type="bibr" rid="B52">&#x106;ilerd&#x17e;i&#x107; et&#xa0;al., 2016a</xref>). <italic>Ganoderma pfeifferi</italic> volatile oil, containing 73.6% 1-octen-3-ol, showed strong antimicrobial activity against <italic>S. aureus</italic> and <italic>C. albicans</italic> along with significant antioxidant capacity (<xref ref-type="bibr" rid="B10">Al-Fatimi et&#xa0;al., 2016</xref>), while <italic>G. lucidum</italic> fermentation broths demonstrated 39.67% antioxidant activity, with strain BEOFB 432 being particularly effective (<xref ref-type="bibr" rid="B53">&#x106;ilerd&#x17e;i&#x107; et&#xa0;al., 2016b</xref>). Kenyan <italic>G. lucidum</italic> extracts exhibited activity against MRSA and common bacteria (up to 10.0 mm inhibition), highlighting its antimicrobial potential (<xref ref-type="bibr" rid="B181">Reid et&#xa0;al., 2016</xref>; <xref ref-type="bibr" rid="B190">Sande and Baraza, 2019</xref>). <italic>Ganoderma tropicum</italic> showed promise as a biocide and corrosion inhibitor against sulfate-reducing bacteria in industrial applications (<xref ref-type="bibr" rid="B224">Stanley et&#xa0;al., 2016</xref>). Comparative studies of eight mushroom species revealed that <italic>G. applanatum</italic>, <italic>Laetiporus sulphureus</italic>, <italic>F. velutipes</italic>, <italic>Trametes versicolor</italic>, <italic>Hericium coralloides</italic>, and <italic>Agaricus campestris</italic> had significant antimicrobial activity against <italic>B. subtilis</italic> ATCC 6633, while <italic>G. lucidum</italic> and <italic>Pleurotus eryngii</italic> showed no effects (<xref ref-type="bibr" rid="B157">Nicolcioiu et&#xa0;al., 2017</xref>). However, <italic>G. lucidum</italic> culture broth demonstrated antibacterial activity against <italic>Staphylococcus epidermidis</italic> and <italic>P. aeruginosa</italic>, suggesting potential for cosmetic and nutraceutical applications (<xref ref-type="bibr" rid="B192">Sarnthima et&#xa0;al., 2017</xref>).</p>
<p>GC-MS analysis of <italic>G. lucidum</italic> mycelia and fruiting bodies revealed that the mycelial aqueous extract possessed the highest anti-<italic>Candida</italic> activity (against <italic>C. albicans</italic> and <italic>C. glabrata</italic> biofilms) and ascorbic acid content, suggesting biofilm prevention potential. Chemometric analysis showed variability in volatile organic compounds between extracts (<xref ref-type="bibr" rid="B32">Bhardwaj et&#xa0;al., 2017</xref>). Antimicrobial testing of <italic>G. lucidum</italic> (GL) showed MICs of 200&#x2013;400 &#xb5;g/mL against <italic>S. aureus</italic>, <italic>E. faecalis</italic>, <italic>L. monocytogenes</italic>, <italic>K. pneumoniae</italic>, <italic>P. aeruginosa</italic>, <italic>E. coli</italic>, and <italic>Candida</italic> spp. While non-cytotoxic to NIH3T3 cells, GL showed genotoxicity (2.71-fold genetic damage at 5 mg/mL) (<xref ref-type="bibr" rid="B71">Ergun, 2017</xref>). <italic>G. lucidum</italic> ethanol extracts showed superior antibacterial activity (lower MICs against <italic>S. aureus</italic>, <italic>M. luteus</italic>, <italic>B. terom</italic>, and <italic>B. subtilis</italic>), while water extracts had higher DPPH scavenging (56.22% vs. 20.67%) (<xref ref-type="bibr" rid="B238">Wang et&#xa0;al., 2017</xref>). Philippine <italic>G. applanatum</italic> and <italic>G. lucidum</italic> ethanol extracts inhibited <italic>S. aureus</italic> (6.55 &#xb1; 0.23 mm to 7.43 &#xb1; 0.29 mm zones) with MIC<sub>50</sub> values of 1,250&#x2013;10,000 &#x3bc;g/mL (<xref ref-type="bibr" rid="B83">Gaylan et&#xa0;al., 2018</xref>). <italic>G. lucidum</italic> extract inhibited MDR <italic>Mycobacterium tuberculosis</italic> (complete inhibition at 25%&#x2013;50% concentration) (<xref ref-type="bibr" rid="B69">Erawati et&#xa0;al., 2018</xref>). Bangladeshi <italic>G. lucidum</italic> exhibited antioxidant activity (IC<sub>50</sub> 89.05 &#xb5;g/mL), cytotoxicity (LC<sub>50</sub> 142.49 &#xb5;g/mL), and antibacterial effects against antibiotic-resistant strains (<xref ref-type="bibr" rid="B96">Islam et&#xa0;al., 2018</xref>). Antimicrobial peptides from <italic>G. lucidum</italic> fruiting bodies (GLF) and mycelium (GLM) showed activity against <italic>E. coli</italic> and <italic>S. typhi</italic> via ROS and protein leakage mechanisms (<xref ref-type="bibr" rid="B138">Mishra et&#xa0;al., 2018a</xref>). <italic>G. lucidum</italic>-based Kombucha beverage achieved 22.8 g/L acidity by day 2, with strong antioxidant/antibacterial activity (especially against <italic>S. epidermidis</italic> and <italic>R. equi</italic>), though the vacuum-dried form was less potent (<xref ref-type="bibr" rid="B217">Sknepnek et&#xa0;al., 2018</xref>).</p>
<p>Australian <italic>G. lucidum</italic> extracts demonstrated significant wound-healing properties, with ethanol/methanol-extracted triterpenes and water-extracted polysaccharides (50 mg/mL) showing antimicrobial activity against <italic>S. aureus</italic> (including MRSA), <italic>B. cereus</italic>, <italic>S. pyogenes</italic>, and <italic>E. coli</italic>. Alkali-extracted compounds were effective against <italic>P. aeruginosa</italic> (<xref ref-type="bibr" rid="B143">Montalbano, 2018</xref>). In food preservation, sausages with 0.5% <italic>G. lucidum</italic> powder maintained lower lipid oxidation and microbial levels while matching sensory acceptability of conventional preservatives (<xref ref-type="bibr" rid="B84">Ghobadi et&#xa0;al., 2018</xref>). <italic>Ganoderma lipsiense</italic> extract specifically inhibited <italic>P. aeruginosa</italic> (via phenolic compounds like caffeic acid) but not <italic>E. coli</italic> or <italic>S. aureus</italic> (<xref ref-type="bibr" rid="B56">Costa et&#xa0;al., 2019</xref>). Turkish <italic>G. lucidum</italic> exhibited high antioxidant potential (TAS/TOS/OSI assays) and antimicrobial activity against nine pathogens (<xref ref-type="bibr" rid="B40">Celal, 2019</xref>). Ethanol extracts (20 g/mL) showed the strongest activity against <italic>S. aureus</italic>, <italic>P. aeruginosa</italic>, and <italic>Fusarium</italic> sp (<xref ref-type="bibr" rid="B230">Tamilselvan and Rajesh, 2019</xref>). Serbian <italic>Ganoderma</italic> species revealed species-specific efficacy: <italic>G. resinaceum</italic> chloroform extract against <italic>P. aeruginosa</italic>, <italic>G. pfeifferi</italic> water extract against <italic>E. coli</italic>/<italic>S. aureus</italic>, and <italic>G. lucidum</italic> showing antiviral potential (<xref ref-type="bibr" rid="B179">Ra&#x161;eta et&#xa0;al., 2023</xref>). South Jakarta <italic>G. lucidum</italic> ethanol extract only affected <italic>S. aureus</italic>, with no dose-dependent improvement (<xref ref-type="bibr" rid="B160">Noverita and Ritchie, 2020</xref>). GC-MS analysis of Nigerian <italic>G. lucidum</italic> identified 48 bioactive compounds (including BHA), with methanol extracts showing the strongest antibacterial effects (except against resistant <italic>P. aeruginosa</italic>) (<xref ref-type="bibr" rid="B17">Anyakorah et&#xa0;al., 2020</xref>). Kenyan studies confirmed <italic>G. lucidum</italic> and <italic>Termitomyces letestui</italic> activity against MRSA and <italic>S. pyogenes</italic> (<xref ref-type="bibr" rid="B18">Anyimba, 2020</xref>). Methanol extracts from Yeast Wine Media completely inhibited fungal growth (500&#x2013;1,000 ppm) and showed superior activity against <italic>Xanthomonas oryzae</italic>/<italic>Ralstonia solanacearum</italic>, with higher antioxidant capacity (<xref ref-type="bibr" rid="B226">Suansia and John, 2021</xref>). Finally, <italic>G. lucidum</italic> methanol extracts exhibited potent antibacterial effects against MDR <italic>E. coli</italic> and <italic>P. aeruginosa</italic> (19.3 &#xb1; 0.4 mm zones, MBC 266 &#xb1; 23.6) (<xref ref-type="bibr" rid="B176">Radhika, 2021</xref>).</p>
<p>Comparative analysis of <italic>G. lucidum</italic> mycelium and spores against <italic>P. intermedia</italic> from periodontitis patients revealed mean MIC values of 5.64 mcg/mL (mycelium) and 3.62 mcg/mL (spores), demonstrating comparable antimicrobial efficacy for adjunct periodontal therapy (<xref ref-type="bibr" rid="B153">Nayak et&#xa0;al., 2021</xref>). Mexican <italic>G. curtisii</italic> strains exhibited notable biological activities, including tumor cell line inhibition (GI<sub>50</sub> &#x2264;50 &#xb5;g/mL), anti-<italic>S. aureus</italic> effects, and antioxidant properties, with strain GH-16&#x2013;023 showing particularly low toxicity (<xref ref-type="bibr" rid="B197">Serrano-M&#xe1;rquez et&#xa0;al., 2021</xref>). Kenyan <italic>G. lucidum</italic> extracts contained terpenoids, phenolics, and glycosides, displaying significant activity against MRSA and <italic>Streptococcus pyogenes</italic>, with the isolated compound Ergosta-5,7,22-triene-3&#x3b2;,14&#x3b1;-diol showing potent antibacterial effects (<xref ref-type="bibr" rid="B25">Baraza et&#xa0;al., 2021</xref>). <italic>G. lucidum</italic> spore powder aqueous extracts demonstrated remarkable antibacterial activity with MIC values of 125 &#xb5;g/mL (<italic>S. aureus</italic> and <italic>E. coli</italic>), &lt;2 &#xb5;g/mL (<italic>E. faecalis</italic>), and 62.5 &#xb5;g/mL (<italic>K. pneumoniae</italic>) (<xref ref-type="bibr" rid="B154">Nayak et&#xa0;al., 2010a</xref>). Comparative studies of <italic>G. boninense</italic> extracts revealed that chloroform-extracted mycelium (GBMA) exhibited the strongest antibacterial activity, particularly through chloroform-methanol-water extraction, suggesting novel antimicrobial metabolites (<xref ref-type="bibr" rid="B2">Abdullah et&#xa0;al., 2020</xref>). Further analysis of <italic>G. boninense</italic> fruiting bodies showed that ethyl acetate extracts had broad-spectrum inhibition (especially against <italic>P. mirabilis</italic>), while methanol extracts showed the lowest MIC (0.625 mg/mL) against Coagulase-Negative Staphylococci, with LC-MS identifying alkaloids, fatty acids, and glycosides as potential bioactive compounds (<xref ref-type="bibr" rid="B42">Chan and Chong, 2020</xref>).</p>
<p>Medicinal polypores including <italic>G. adspersum</italic>, <italic>G. applanatum</italic>, and <italic>G. australe</italic> yielded bioactive ergostane compounds (ergosta-7,22-dien-3-one and ergosta-7,22-diene-3&#x3b2;-ol) through methanol/ethyl acetate extractions, showing significant inhibition against <italic>S. pyogenes</italic> but not Gram-negative bacteria, suggesting potential for novel myco-medicines (<xref ref-type="bibr" rid="B133">Mayaka, 2020</xref>). In biofilm-related studies, <italic>G. lucidum</italic> demonstrated notable anti-biofilm activity against multidrug-resistant (MDR) <italic>Enterococcus</italic> strains, offering alternatives for challenging infections (<xref ref-type="bibr" rid="B106">Karaca et&#xa0;al., 2020</xref>). Phytochemical analysis revealed that wild <italic>Ganoderma</italic> species contained saponins and flavonoids, with <italic>G. lucidum</italic> showing the highest cyanide content. Ethanolic extracts inhibited <italic>Salmonella</italic> spp., <italic>E. coli</italic>, <italic>S. aureus</italic>, and <italic>Streptococcus</italic> spp., with <italic>G. applanatum</italic> particularly effective against <italic>E. coli</italic> (19.50 mg/mL) and all species showing similar MBC (~250 mg/mL) (<xref ref-type="bibr" rid="B242">Wood et&#xa0;al., 2021</xref>). Optimized cultivation of Philippine <italic>G. lucidum</italic> on sawdust/PDA yielded ethanol extracts (100&#x2013;200 mg/mL) that outperformed standard antibiotics in antibacterial tests, with fruiting bodies showing superior antioxidant activity to mycelia (<xref ref-type="bibr" rid="B228">Subedi et&#xa0;al., 2021</xref>). Nine <italic>Ganoderma</italic> species extracts, including <italic>G. tuberculosum</italic> and <italic>G. tornatum</italic>, inhibited <italic>Clavibacter michiganensis</italic> (31.5&#x2013;1,000 &#x3bc;g/mL), suggesting applications for tomato canker management (<xref ref-type="bibr" rid="B72">Espinosa-Garc&#xed;a et&#xa0;al., 2021</xref>).</p>
<p>Comparative studies of medicinal mushrooms revealed that <italic>Taiwanofungus camphoratus</italic> methanolic extracts showed strong antimicrobial activity, while <italic>G. lucidum</italic> extracts displayed no significant effects, with concerns about <italic>Penicillium expansum</italic> developing tolerance (<xref ref-type="bibr" rid="B114">Kim et&#xa0;al., 2022</xref>). <italic>G. boninense</italic> demonstrated exceptional anti-MRSA activity (41.08 mm zone, MIC 0.078 mg/mL) through membrane disruption, with LC-MS identifying eight bioactive compounds (<xref ref-type="bibr" rid="B43">Chan and Chong, 2022</xref>). Iraqi studies showed that <italic>G. lucidum</italic> methanol extract (200 mg/mL) was most effective against UTI pathogens (<italic>K. pneumoniae</italic>, <italic>S. aureus</italic>, and <italic>P. mirabilis</italic>), containing flavonoids, alkaloids, phenols, and terpenoids (<xref ref-type="bibr" rid="B205">Shawkat and Aedan, 2022</xref>). Metabolite profiling of six <italic>Ganoderma</italic> species identified <italic>G. pfeifferi</italic> as the richest in phenolic acids (114.07 mg/100 g DW) and <italic>G. lucidum</italic> as the richest in indole compounds, with all showing antioxidant and enzyme inhibitory potential (<xref ref-type="bibr" rid="B229">Su&#x142;kowska-Ziaja et&#xa0;al., 2022</xref>). <italic>G. lucidum</italic> methanol extract demonstrated dual anti-MRSA activity <italic>in vitro</italic> and <italic>in vivo</italic>, reducing lung inflammation and LDH levels in infected rats (<xref ref-type="bibr" rid="B222">Soliman et&#xa0;al., 2022</xref>). Moroccan studies revealed the potent antimicrobial activity of <italic>G. lucidum</italic> extract (especially against <italic>Epidermophyton floccosum</italic>) and high phenolic/flavonoid content (<xref ref-type="bibr" rid="B70">Erbiai et&#xa0;al., 2023</xref>). Further studies confirmed antimicrobial (MIC 50 &#x3bc;g/mL against <italic>S. aureus/E. coli</italic>) and antioxidant (85.9%&#x2013;90.12% radical scavenging at 400 &#x3bc;g/mL) properties of <italic>G. lucidum</italic> (<xref ref-type="bibr" rid="B231">Tehranian et&#xa0;al., 2023</xref>). Turkish specimens showed 90.81% DPPH scavenging and notable anti-<italic>E. faecalis</italic> activity (17.67 &#xb1; 0.47 mm zone), with GC-MS identifying key fatty acids (<xref ref-type="bibr" rid="B39">Canpolat and Canpolat, 2023</xref>). <italic>Ganoderma mbrekobenum</italic> methanol extracts showed strong anti-<italic>Bacillus</italic> (15- to 18-mm zones) and anti-<italic>Fusarium</italic> activity, with 46 bioactive compounds identified (<xref ref-type="bibr" rid="B63">El-Dein et&#xa0;al., 2023</xref>). Antifungal studies demonstrated that <italic>G. lucidum</italic> pure extract achieved 100% inhibition of <italic>Colletotrichum gloeosporioides</italic> and 94.4% against <italic>Alternaria solani</italic> (<xref ref-type="bibr" rid="B188">Saludares et&#xa0;al., 2023</xref>). Comparative analysis showed that <italic>G. lucidum</italic> surpassed <italic>G. neo-japonicum</italic> in protein content (24.3 vs. 15.6 mg/g), phenolics (14.3 vs. 9.8 mg GAE/g), and antioxidant capacity (FRAP 403.9 &#x3bc;mol Fe<sup>2+</sup>/g) (<xref ref-type="bibr" rid="B20">Ayimbila et&#xa0;al., 2023</xref>). The extraction method significantly influenced bioactivity&#x2014;Soxhlet ethanol extracts showed strongest anticancer effects (MCF-7 IC<sub>50</sub> 4.797 &#x3bc;g/mL) while UAE water extracts had the best anti-<italic>S. aureus</italic> activity (20&#x2013;23 mm) (<xref ref-type="bibr" rid="B21">Azahar et&#xa0;al., 2023</xref>).</p>
</sec>
<sec id="s5_1_2">
<label>5.1.2</label>
<title>Triterpenoids</title>
<p>Infectious diseases caused by bacteria, fungi, viruses, and parasites remain a leading cause of global morbidity and mortality, particularly in low- and middle-income countries. The rise of AMR, emerging viral pathogens, and neglected tropical diseases underscores the urgent need for new therapeutic agents. <italic>Ganoderma</italic> species, especially through their triterpenoid-rich extracts, represent a promising yet underutilized resource in addressing these critical health challenges. Triterpenoids, particularly lanostane-type compounds, are among the most bioactive secondary metabolites in <italic>Ganoderma</italic> spp., exhibiting broad-spectrum antimicrobial and antiviral activity (<xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>). Their multifaceted mechanisms include membrane disruption, enzyme inhibition, and immunomodulation.</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>Antimicrobial properties of triterpenoids in <italic>Ganoderma</italic> species.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Species</th>
<th valign="top" align="left">Key compounds/extracts</th>
<th valign="top" align="left">Key findings</th>
<th valign="top" align="left">Activity indicator</th>
<th valign="top" align="left">Disease relevance/Target pathogens</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" rowspan="3" align="left">
<italic>Ganoderma lucidum</italic>
</td>
<td valign="top" align="left">Ganoderic acids GA-T and GA-Me</td>
<td valign="top" align="left">Antibacterial and antifungal activity</td>
<td valign="top" align="left">MIC: 150 &#xb5;g/mL (bacteria), 100 &#xb5;g/mL (fungi)</td>
<td valign="top" align="left">Potential use in treating dermatomycoses, respiratory infections, and Gram-positive sepsis</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B213">Shveta et&#xa0;al., 2013</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Triterpenoid extract from GLSP</td>
<td valign="top" align="left">Inhibits <italic>S. aureus</italic> and <italic>E. coli</italic>
</td>
<td valign="top" align="left">61.09% DPPH inhibition</td>
<td valign="top" align="left">Relevance to skin and urinary tract infections (UTIs)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B207">Shen et&#xa0;al., 2020</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Ethanolic extract (lanostanoid ester)</td>
<td valign="top" align="left">Active against <italic>S. aureus</italic> and <italic>B. subtilis</italic>
</td>
<td valign="top" align="left">MIC 68.5 &#xb5;M (<italic>S. aureus</italic>), 123.8 &#xb5;M (<italic>B. subtilis</italic>)</td>
<td valign="top" align="left">Relevance to hospital-acquired infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B126">Liu et&#xa0;al., 2014</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">
<italic>G. applanatum</italic>
</td>
<td valign="top" align="left">Lanostanoids, sterols</td>
<td valign="top" align="left">Broad antibacterial spectrum</td>
<td valign="top" align="left">MIC: 0.003&#x2013;2.0 mg/mL; MBC: 0.06&#x2013;4.0 mg/mL</td>
<td valign="top" align="left">Targets respiratory tract bacteria; potential for topical wound infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B220">Smania et&#xa0;al., 1999</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Lanostane triterpenoids</td>
<td valign="top" align="left">Notable antimicrobial effects</td>
<td valign="top" align="left">&lt;60 &#x3bc;g/mL</td>
<td valign="top" align="left">Relevance to cutaneous fungal infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B209">Shi et&#xa0;al., 2022</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. casuarinicola</italic>
</td>
<td valign="top" align="left">Norlanostanes, ganocasuarinone A</td>
<td valign="top" align="left">Active against <italic>S. aureus</italic> and <italic>M. tuberculosis</italic>
</td>
<td valign="top" align="left">5 mg/mL (<italic>S. aureus</italic>), 25&#x2013;50 &#xb5;g/mL (<italic>M. tuberculosis</italic>)</td>
<td valign="top" align="left">Relevance to tuberculosis and Gram-positive infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B95">Isaka et&#xa0;al., 2020</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Early studies on <italic>G. applanatum</italic> identified three sterols and a novel lanostanoid with potent antibacterial activity, showing Gram-positive specificity (MIC: 0.003&#x2013;2.0 mg/mL; MBC: 0.06&#x2013;4.0 mg/mL) (<xref ref-type="bibr" rid="B220">Smania et&#xa0;al., 1999</xref>). Nigerian <italic>G. colossum</italic> yielded new colossolactones including 23-hydroxycolossolactone E with antimicrobial potential (<xref ref-type="bibr" rid="B164">Ofodile et&#xa0;al., 2005</xref>). Modified applanoxidic acids from <italic>Ganoderma</italic> spp. maintained activity against <italic>E. coli</italic>, <italic>S. aureus</italic>, <italic>C. albicans</italic>, and <italic>T. mentagrophytes</italic> (MIC: 1.0 to &gt;2.0 mg/mL) (<xref ref-type="bibr" rid="B221">Smania et&#xa0;al., 2006</xref>). Western Ghats <italic>Ganoderma</italic> sesquiterpenoids surpassed standard antibiotics against bacteria and <italic>C. albicans</italic>, while triterpenes showed weaker effects (<xref ref-type="bibr" rid="B34">Bhosle et&#xa0;al., 2010</xref>). Colossolactones E and 23-hydroxycolossolactone E demonstrated activity against <italic>B. subtilis</italic> and <italic>P. syringae</italic> (<xref ref-type="bibr" rid="B162">Ofodile et&#xa0;al., 2011</xref>), with <italic>G. lucidum</italic> and <italic>G. mazandaran</italic> showing the lowest MICs (128 &#xb5;l/mL) against <italic>B. subtilis</italic> and <italic>P. mirabilis</italic> (<xref ref-type="bibr" rid="B163">Ofodile et&#xa0;al., 2012</xref>). Haryana <italic>G. lucidum</italic> yielded ganoderic acids (GA-T and GA-Me) with MICs of 150 &#xb5;g/mL (bacteria) and 100 &#xb5;g/mL (fungi) (<xref ref-type="bibr" rid="B213">Shveta et&#xa0;al., 2013</xref>). <italic>Ganoderma</italic> sp. BCC 16,642 produced ganoderic acids/lanostanoids active against <italic>S. aureus</italic> and <italic>B. subtilis</italic> (<xref ref-type="bibr" rid="B126">Liu et&#xa0;al., 2014</xref>). Ethyl acetate extracts of <italic>G. lucidum</italic> contained novel antimicrobial triterpenoids (<xref ref-type="bibr" rid="B126">Liu et&#xa0;al., 2014</xref>), while its GA showed cytotoxicity and antibacterial effects (<xref ref-type="bibr" rid="B232">Upadhyay et&#xa0;al., 2014</xref>). Two triterpenoids (GLTA and GLTB) exhibited anti-EV71 activity by blocking viral adsorption and RNA replication (<xref ref-type="bibr" rid="B251">Zhang et&#xa0;al., 2014</xref>). <italic>Ganoderma</italic> triterpenoids inhibited <italic>S. aureus</italic> biofilms and <italic>E. coli</italic> (<xref ref-type="bibr" rid="B28">Basnet et&#xa0;al., 2017</xref>). Recent studies revealed that <italic>G. lucidum</italic> spore powder triterpenoids had 61.09% DPPH inhibition (600 &#xb5;g/mL) and anti-<italic>S. aureus/E. coli</italic> activity (<xref ref-type="bibr" rid="B207">Shen et&#xa0;al., 2020</xref>). <italic>Ganoderma casuarinicola</italic> norlanostanes showed anti-<italic>S. aureus</italic> (5 mg/mL) and anti-TB (25&#x2013;50 &#xb5;g/mL) effects (<xref ref-type="bibr" rid="B95">Isaka et&#xa0;al., 2020</xref>). <italic>G. applanatum</italic> yielded three new antimicrobial lanostane triterpenoids (<xref ref-type="bibr" rid="B209">Shi et&#xa0;al., 2022</xref>). Given their demonstrated efficacy against MDR bacteria (e.g., MRSA), biofilm-producing strains, and even viruses, <italic>Ganoderma</italic>-derived triterpenoids offer a compelling lead for drug discovery targeting difficult-to-treat infections. Their ability to address current gaps in antifungal and antiviral therapeutics, coupled with favorable safety profiles in traditional use, reinforces their potential for clinical translation. <xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref> provides an overview of the antibacterial properties exhibited by various extracts of Ganoderma species.</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Overview of antibacterial properties in <italic>Ganoderma</italic> extracts.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Species</th>
<th valign="top" align="left">Extract type</th>
<th valign="top" align="left">Key findings</th>
<th valign="top" align="left">Potential applications/Disease relevance</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" rowspan="2" align="left">
<italic>Ganoderma applanatum</italic>
</td>
<td valign="top" align="left">Methanol/Methanolic/Ethanolic</td>
<td valign="top" align="left">Strong activity against Gram-positive bacteria and some fungi; phenolic-rich</td>
<td valign="top" align="left">Potential treatment for skin infections, respiratory infections, and Gram-positive sepsis in humans and animals</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B174">Pushpa et&#xa0;al., 2013</xref>; <xref ref-type="bibr" rid="B144">Moradali et&#xa0;al., 2008</xref>; <xref ref-type="bibr" rid="B57">Dandapat et&#xa0;al., 2016</xref>; <xref ref-type="bibr" rid="B182">Rijia et&#xa0;al., 2024</xref>; <xref ref-type="bibr" rid="B83">Gaylan et&#xa0;al., 2018</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Extracts</td>
<td valign="top" align="left">Highest antibacterial and antifungal activity</td>
<td valign="top" align="left">Potential for broad-spectrum antimicrobial therapies</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B127">Lone et&#xa0;al., 2024</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. boninense</italic>
</td>
<td valign="top" align="left">Methanol/Ethyl acetate/Chloroform</td>
<td valign="top" align="left">Broad-spectrum activity, including MRSA; membrane disruption</td>
<td valign="top" align="left">Wound infections, multidrug-resistant bacterial infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B97">Ismail et&#xa0;al., 2014</xref>; <xref ref-type="bibr" rid="B42">Chan and Chong, 2020</xref>, <xref ref-type="bibr" rid="B43">2022</xref>; <xref ref-type="bibr" rid="B2">Abdullah et&#xa0;al., 2020</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. carnosum</italic>
</td>
<td valign="top" align="left">Dichloromethane extracts</td>
<td valign="top" align="left">Antibacterial and antifungal; antioxidant properties</td>
<td valign="top" align="left">Topical antimicrobials, antifungal creams, plant protection</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B223">Srivastava and Sharma, 2011</xref>; <xref ref-type="bibr" rid="B229">Su&#x142;kowska-Ziaja et&#xa0;al., 2022</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. colossus</italic>
</td>
<td valign="top" align="left">Dichloromethane, Methanolic, Water</td>
<td valign="top" align="left">Effective against <italic>E. coli</italic> and <italic>S. aureus</italic>
</td>
<td valign="top" align="left">Gastrointestinal and skin infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B9">Al-Fatimi et&#xa0;al., 2005</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. curtisii</italic>
</td>
<td valign="top" align="left">Extracts</td>
<td valign="top" align="left">Antiproliferative, antioxidant, and antibacterial effects</td>
<td valign="top" align="left">Immunocompromised patient care, supportive cancer therapy</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B197">Serrano-M&#xe1;rquez et&#xa0;al., 2021</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">Multiple solvents</td>
<td valign="top" align="left">Broad antimicrobial activity; quorum sensing inhibition</td>
<td valign="top" align="left">Anti-biofilm agent in chronic respiratory or wound infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B75">Fakoya et&#xa0;al., 2013</xref>; <xref ref-type="bibr" rid="B85">Gowrie et&#xa0;al., 2014</xref>; <xref ref-type="bibr" rid="B202">Shang et&#xa0;al., 2013</xref>; <xref ref-type="bibr" rid="B257">Zhu et&#xa0;al., 2011</xref>; others</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. tsugae</italic>
</td>
<td valign="top" align="left">Chitosan extracts</td>
<td valign="top" align="left">Strong antibacterial, surpassing doxycycline</td>
<td valign="top" align="left">Acne treatment, resistant skin infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B46">Chen et&#xa0;al., 2007</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. resinaceum</italic>
</td>
<td valign="top" align="left">Dichloromethane, Methanolic, Water</td>
<td valign="top" align="left">Active against several bacterial pathogens</td>
<td valign="top" align="left">Alternative to conventional antibiotics</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B9">Al-Fatimi et&#xa0;al., 2005</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. tuberculosum</italic>, <italic>G. tornatum</italic>, <italic>G. weberianum</italic>
</td>
<td valign="top" align="left">Chloroform-methanol extracts</td>
<td valign="top" align="left">Antibacterial against <italic>Clavibacter michiganensis</italic>
</td>
<td valign="top" align="left">Crop disease biocontrol (e.g., tomato canker)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B72">Espinosa-Garc&#xed;a et&#xa0;al., 2021</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>Ganoderma</italic> spp.</td>
<td valign="top" align="left">Various solvents</td>
<td valign="top" align="left">Antibacterial and antifungal against human/plant pathogens</td>
<td valign="top" align="left">Agricultural biopesticide or general therapeutic candidate</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B246">Yamac and Bilgili, 2006</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s5_1_3">
<label>5.1.3</label>
<title>Polysaccharides</title>
<p>Polysaccharides from <italic>Ganoderma</italic> species, particularly <italic>G. lucidum</italic>, offer compelling bioactivity that aligns with global efforts to combat infectious diseases. As AMR and gastrointestinal infections continue to rise globally, especially in immunocompromised populations and developing regions, the need for non-antibiotic, immune-enhancing alternatives becomes critical. <italic>Ganoderma</italic>-derived polysaccharides, rich in &#x3b2;-glucans and heteropolysaccharides, are emerging as promising immunomodulatory and antimicrobial agents that could complement or replace conventional antimicrobials (<xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>).</p>
<table-wrap id="T3" position="float">
<label>Table&#xa0;3</label>
<caption>
<p>Polysaccharides in <italic>Ganoderma</italic> species and their antimicrobial properties.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">
<italic>Ganoderma</italic> species</th>
<th valign="top" align="left">Polysaccharide composition</th>
<th valign="top" align="left">Pathogens targeted</th>
<th valign="top" align="left">Disease relevance/Target infection</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" rowspan="9" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">D-glucose-based polysaccharides</td>
<td valign="top" align="left">Plant and foodborne microbes</td>
<td valign="top" align="left">Foodborne infections, gastrointestinal illness</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B23">Bai et&#xa0;al., 2008</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">Gram-positive bacteria</td>
<td valign="top" align="left">Skin infections, respiratory pathogens</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B216">Skalicka-Wozniak et&#xa0;al., 2012</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">Bacterial pathogens</td>
<td valign="top" align="left">General bacterial infections in humans</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B29">Batra and Khajuria, 2012</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Exopolysaccharides (EPS)</td>
<td valign="top" align="left">
<italic>Bacillus cereus</italic>
</td>
<td valign="top" align="left">Food poisoning, diarrheal syndromes</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B130">Mahendran et&#xa0;al., 2013</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">Opportunistic bacteria</td>
<td valign="top" align="left">Hospital-acquired infections (e.g., wound and lung)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B111">Kaur et&#xa0;al., 2015</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">(1,3)-&#x3b2;-D-glucan, GS</td>
<td valign="top" align="left">Foodborne and clinical strains</td>
<td valign="top" align="left">Enteric infections, sepsis-related strains</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B240">Wan-Mohtar et&#xa0;al., 2016</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Chitosan</td>
<td valign="top" align="left">Gram-positive cocci</td>
<td valign="top" align="left">Skin and bloodstream infections (e.g., <italic>S. aureus</italic>)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B194">Savin et&#xa0;al., 2020</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Low-MW polysaccharides (3.5&#x2013;4.5 kDa)</td>
<td valign="top" align="left">Agricultural pathogens</td>
<td valign="top" align="left">Zoonotic bacterial risks through crops</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B184">Robles-Hern&#xe1;ndez et&#xa0;al., 2021</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">
<italic>E. coli</italic> strain</td>
<td valign="top" align="left">Gastrointestinal infections and UTIs</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B249">Zhai et&#xa0;al., 2021</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. multicornum</italic>, <italic>G. multiplicatum</italic>, <italic>G. perzonatum</italic>, and <italic>G. stipitatum</italic>
</td>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">Enteric bacteria</td>
<td valign="top" align="left">Diarrheal diseases in livestock and humans</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B203">Sharifi et&#xa0;al., 2012</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Various <italic>Ganoderma</italic> spp.</td>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">Mixed bacterial species</td>
<td valign="top" align="left">Broad-spectrum infections (foodborne, respiratory)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B9">Al-Fatimi et&#xa0;al., 2005</xref>; <xref ref-type="bibr" rid="B94">Isaka et&#xa0;al., 2016</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Hot water extracts of <italic>G. lucidum</italic> fruiting bodies, primarily composed of D-glucose, have demonstrated activity against plant pathogens (<italic>Erwinia carotovora</italic> and <italic>Penicillium digitatum</italic>) and foodborne microbes (<italic>B. cereus</italic>, <italic>E. coli</italic>, and <italic>Aspergillus niger</italic>) (<xref ref-type="bibr" rid="B23">Bai et&#xa0;al., 2008</xref>). <italic>G. lucidum</italic> polysaccharides also strongly inhibit <italic>M. luteus</italic> (MIC 0.62&#x2013;1.25 mg/mL) (<xref ref-type="bibr" rid="B216">Skalicka-Wozniak et&#xa0;al., 2012</xref>), and fractions isolated from <italic>G. multicornum</italic> and related species show activity against <italic>E. coli</italic> and <italic>P. mirabilis</italic> (<xref ref-type="bibr" rid="B203">Sharifi et&#xa0;al., 2012</xref>). Additional studies revealed inhibition zones up to 19 mm against <italic>Staphylococcus</italic> sp. (<xref ref-type="bibr" rid="B29">Batra and Khajuria, 2012</xref>) and potent activity (18- to 23-mm inhibition zones) from exopolysaccharides (EPS) cultivated on basal and malt media (<xref ref-type="bibr" rid="B130">Mahendran et&#xa0;al., 2013</xref>). Strain-specific studies showed that <italic>G. lucidum</italic> GL-2 and GL-3 produce polysaccharides that inhibit <italic>Staphylococcus</italic> and <italic>Enterobacter</italic> spp (<xref ref-type="bibr" rid="B111">Kaur et&#xa0;al., 2015</xref>). Mechanistically, these polysaccharides exert their antimicrobial action by disrupting microbial cell walls and modulating oxidative stress. Their synergy with phenolic compounds enhances antimicrobial efficacy, suggesting a multi-targeted mode of action (<xref ref-type="bibr" rid="B9">Al-Fatimi et&#xa0;al., 2005</xref>; <xref ref-type="bibr" rid="B94">Isaka et&#xa0;al., 2016</xref>).</p>
<p>
<italic>G. lucidum</italic> strain BCCM 31549 produces both (1,3)-&#x3b2;-D-glucan (G) and its sulfated derivative (GS), with GS exhibiting not only superior antimicrobial activity but also selective cytotoxicity against <italic>U937</italic> cancer cells (<xref ref-type="bibr" rid="B240">Wan-Mohtar et&#xa0;al., 2016</xref>), pointing to potential dual anti-infective and anticancer utility. Enzymatically extracted chitosan from <italic>G. lucidum</italic> shows superior antibacterial effects against Gram-positive bacteria and improved antioxidant activity compared to chemically extracted counterparts (<xref ref-type="bibr" rid="B194">Savin et&#xa0;al., 2020</xref>). Small-molecular-weight polysaccharides (3,500&#x2013;4,500 Da) isolated from culture fluids have recently demonstrated strong antibacterial effects against plant pathogens (<xref ref-type="bibr" rid="B184">Robles-Hern&#xe1;ndez et&#xa0;al., 2021</xref>), offering a sustainable source for agricultural biocontrol. In a more clinically relevant context, <italic>G. lucidum</italic> polysaccharides at concentrations of 5&#x2013;100 &#x3bc;g/mL not only inhibited <italic>E. coli</italic> proliferation but also modulated immune response pathways in intestinal porcine epithelial cells (IPEC-1), suggesting potential for treating or preventing bacterial gut infections (<xref ref-type="bibr" rid="B249">Zhai et&#xa0;al., 2021</xref>).</p>
<p>Collectively, these findings suggest that <italic>Ganoderma</italic> polysaccharides can address important global health challenges such as antibiotic-resistant bacterial infections, especially gastrointestinal and foodborne diseases. Their natural origin, immunostimulatory properties, and low toxicity support their further development as functional antimicrobial agents or as adjuncts to conventional therapies.</p>
</sec>
<sec id="s5_1_4">
<label>5.1.4</label>
<title>Other compounds</title>
<p>In addition to triterpenoids and polysaccharides, <italic>Ganoderma</italic> species produce a chemically diverse repertoire of secondary metabolites&#x2014;including essential oils, steroids, phenolics, alkaloids, and proteins&#x2014;that contribute to their antimicrobial properties (<xref ref-type="table" rid="T4">
<bold>Table&#xa0;4</bold>
</xref>). These compounds are increasingly viewed as promising leads in the search for novel anti-infective agents, particularly against MDR pathogens. Given the growing global burden of AMR, notably <italic>S. aureus</italic>, <italic>M. tuberculosis</italic>, and nosocomial Gram-negative infections, such natural compounds represent a valuable reservoir for alternative therapies and adjunct treatments. Essential oils derived from <italic>G. japonicum</italic> mycelia, rich in nerolidol and linalool, exhibited potent activity against MRSA, with a minimum bactericidal concentration (MBC) of 1.03 mg/mL (<xref ref-type="bibr" rid="B124">Liu et&#xa0;al., 2009</xref>). <italic>G. pfeifferi</italic> produced ganomycins A and B, which demonstrated pronounced anti-Gram-positive activity (MIC 2.5&#x2013;25 &#xb5;g/mL) (<xref ref-type="bibr" rid="B146">Mothana et&#xa0;al., 2000</xref>), suggesting potential as topical agents or adjuvants for skin and wound infections. Novel metabolites from <italic>G. australe</italic>, including australic acid, showed broad-spectrum antimicrobial effects (<xref ref-type="bibr" rid="B219">Smania et&#xa0;al., 2007</xref>), while solvent extracts of <italic>G. lucidum</italic> yielded terpenoids, alkaloids, and steroids with wide-ranging antimicrobial activity (<xref ref-type="bibr" rid="B227">Subbraj et&#xa0;al., 2008</xref>). Proteinaceous extracts from <italic>G. resinaceum</italic> also demonstrated notable activity against hospital-associated pathogens, including <italic>E. coli</italic>, <italic>S. aureus</italic>, and <italic>K. pneumoniae</italic> (<xref ref-type="bibr" rid="B88">Hearst et&#xa0;al., 2010</xref>), while <italic>G. lucidum</italic> extracts produced inhibition zones up to 16 mm against MDR clinical isolates (<xref ref-type="bibr" rid="B195">Sekaran et&#xa0;al., 2011</xref>). Steroidal compounds from several <italic>Ganoderma</italic> species were shown to inhibit <italic>M. tuberculosis</italic> (MIC 0.781&#x2013;50 &#xb5;g/mL) and Gram-positive cocci (<xref ref-type="bibr" rid="B235">Vazirian et&#xa0;al., 2014</xref>), underscoring their relevance for neglected and resurgent infectious diseases such as tuberculosis. Innovative processing and analytical techniques have recently advanced the identification of bioactives from <italic>Ganoderma</italic>. Gamma irradiation enhanced the antimicrobial potency of <italic>G. resinaceum</italic> (<xref ref-type="bibr" rid="B1">Abd El-Zaher, 2010</xref>), while LC-MS analysis detected bioactive compounds such as hesperetin and ganocin B in <italic>G. lucidum</italic> (<xref ref-type="bibr" rid="B3">Abdullah et&#xa0;al., 2021</xref>). Optimized extraction protocols yielded phenolic-rich fractions (16.01 mg/g total phenolics) from <italic>G. lucidum</italic>, which showed potent activity against <italic>S. aureus</italic> (10.6-mm inhibition zone) (<xref ref-type="bibr" rid="B132">Masjedi et&#xa0;al., 2022</xref>). These effects are partly attributed to ROS-mediated bacterial protein leakage, as evidenced by phenolic fractions of <italic>G. lucidum</italic> (<xref ref-type="bibr" rid="B139">Mishra et&#xa0;al., 2018b</xref>). Moreover, uncooked <italic>Ganoderma</italic> biomass has shown dual antimicrobial and anticancer activity, offering potential for functional food or nutraceutical applications (<xref ref-type="bibr" rid="B11">Alghonaim et&#xa0;al., 2023</xref>). Altogether, these studies reveal that non-triterpenoid <italic>Ganoderma</italic> metabolites&#x2014;especially essential oils, phenolics, and proteins&#x2014;may offer novel solutions to combat AMR and opportunistic infections. However, their clinical translation remains limited due to a lack of <italic>in vivo</italic> validation, pharmacokinetic profiling, and toxicity assessments. Future work should prioritize preclinical testing of these compounds in infection models, particularly for high-burden diseases such as tuberculosis, hospital-acquired infections, and drug-resistant enteric pathogens.</p>
<table-wrap id="T4" position="float">
<label>Table&#xa0;4</label>
<caption>
<p>Antimicrobial properties of various other compounds isolated from <italic>Ganoderma</italic> species.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">
<italic>Ganoderm</italic>a sp.</th>
<th valign="top" align="left">Main bioactive components</th>
<th valign="top" align="left">Pathogens targeted</th>
<th valign="top" align="left">Disease relevance/Target infection</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">
<italic>Ganoderma atrum</italic>
</td>
<td valign="top" align="left">Sterols</td>
<td valign="top" align="left">Oxidative protection in Caco-2 cells</td>
<td valign="top" align="left">Intestinal epithelial protection, gut inflammation</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B86">Guo et&#xa0;al., 2022</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. australe</italic>
</td>
<td valign="top" align="left">Australic acid and methyl australate</td>
<td valign="top" align="left">Gram-positive and Gram-negative bacteria, fungi</td>
<td valign="top" align="left">Broad-spectrum antimicrobial for skin and internal infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B219">Smania et&#xa0;al., 2007</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. boninense</italic>
</td>
<td valign="top" align="left">Ergosterol and ganoboninketals</td>
<td valign="top" align="left">
<italic>S. aureus</italic> strains</td>
<td valign="top" align="left">Skin infections, pneumonia, endocarditis</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B3">Abdullah et&#xa0;al., 2021</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. japonicum</italic>
</td>
<td valign="top" align="left">Nerolidol, linalool, decadienal, and benzyl alcohol</td>
<td valign="top" align="left">18 microorganisms, especially MRSA</td>
<td valign="top" align="left">Multidrug-resistant infections (e.g., MRSA in hospitals)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B124">Liu et&#xa0;al., 2009</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="4" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">Steroids, terpenoids, and alkaloids</td>
<td valign="top" align="left">Gram-positive bacteria</td>
<td valign="top" align="left">Respiratory and skin infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B227">Subbraj et&#xa0;al., 2008</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Phenolic compounds</td>
<td valign="top" align="left">Pathogenic bacteria</td>
<td valign="top" align="left">General bacterial infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B139">Mishra et&#xa0;al., 2018b</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Tannins, phenolics, flavonoids, and saponins</td>
<td valign="top" align="left">
<italic>P. aeruginosa</italic>, <italic>E. coli</italic>, <italic>S. aureus</italic>, and <italic>K. pneumoniae</italic>
</td>
<td valign="top" align="left">Wound infections, UTIs, and nosocomial pathogens</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B195">Sekaran et&#xa0;al., 2011</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Uncooked biomass</td>
<td valign="top" align="left">Antimicrobial and anticancer (MCF-7 cells)</td>
<td valign="top" align="left">Breast cancer and general microbial infection</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B11">Alghonaim et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">
<italic>G. resinaceum</italic>
</td>
<td valign="top" align="left">Peptides</td>
<td valign="top" align="left">
<italic>E. coli</italic>, MRSA, and <italic>Salmonella</italic>
</td>
<td valign="top" align="left">Gastrointestinal and systemic infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B88">Hearst et&#xa0;al., 2010</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Lipids</td>
<td valign="top" align="left">
<italic>Fusarium oxysporum</italic> and <italic>Candida albicans</italic>
</td>
<td valign="top" align="left">Mycotic infections in humans and animals</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B1">Abd El-Zaher, 2010</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="3" align="left">
<italic>Ganoderma</italic> spp.</td>
<td valign="top" align="left">Ganomycins A and B</td>
<td valign="top" align="left">
<italic>S. aureus</italic> and <italic>Micrococcus flavus</italic>
</td>
<td valign="top" align="left">Gram-positive infections in skin and soft tissue</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B146">Mothana et&#xa0;al., 2000</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Steroidal compounds</td>
<td valign="top" align="left">
<italic>Mycobacterium tuberculosis</italic>, <italic>S. aureus</italic>, and <italic>B. subtilis</italic>
</td>
<td valign="top" align="left">Tuberculosis and staph-related infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B235">Vazirian et&#xa0;al., 2014</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Multiple compounds</td>
<td valign="top" align="left">
<italic>P. aeruginosa</italic>, <italic>S. typhimurium</italic>, and <italic>K. pneumoniae</italic>
</td>
<td valign="top" align="left">GI, respiratory, and opportunistic infections</td>
<td valign="top" align="left">
</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s5_1_5">
<label>5.1.5</label>
<title>Nanoparticles</title>
<p>The global rise of AMR and chronic biofilm-associated infections underscores the urgent need for novel, multi-targeted therapeutics that are both effective and sustainable. Nanotechnology has emerged as a powerful tool in this arena, and <italic>Ganoderma</italic>-derived nanoparticles&#x2014;particularly silver nanoparticles (Ag-NPs)&#x2014;represent a promising frontier in fungal biomedicine. Infections caused by MDR pathogens such as <italic>S. aureus</italic>, <italic>E. coli</italic>, and <italic>P. aeruginosa</italic> remain major contributors to mortality in hospitals worldwide, with the WHO designating these as &#x201c;priority pathogens.&#x201d; Numerous studies have demonstrated that Ag-NPs synthesized from <italic>G. lucidum</italic>, <italic>G. resinaceum</italic>, and <italic>G. sessile</italic> exhibit broad-spectrum antibacterial activity, often surpassing the efficacy of conventional antibiotics or potentiating their effects through synergistic mechanisms (<xref ref-type="bibr" rid="B105">Kannan et&#xa0;al., 2014</xref>; <xref ref-type="bibr" rid="B12">Ali Syed et&#xa0;al., 2023</xref>; <xref ref-type="table" rid="T5">
<bold>Table&#xa0;5</bold>
</xref>).</p>
<table-wrap id="T5" position="float">
<label>Table&#xa0;5</label>
<caption>
<p>Overview of antimicrobial activity and applications of nanoparticles derived from <italic>Ganoderma</italic> species.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">
<italic>Ganoderm</italic>a species</th>
<th valign="top" align="left">Nanoparticle type</th>
<th valign="top" align="left">Antimicrobial activity</th>
<th valign="top" align="left">Additional applications</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" rowspan="3" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">Silver (Ag-NPs)</td>
<td valign="top" align="left">Active vs. <italic>S. aureus</italic>, <italic>E. coli</italic>, and <italic>P. aeruginosa</italic>; enhances antibiotics</td>
<td valign="top" align="left">Therapeutic, anticancer (IC<sub>50</sub> 9.2 &#xb5;g/mL), wound dressings, and public health</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B105">Kannan et&#xa0;al., 2014</xref>; <xref ref-type="bibr" rid="B8">Al-Ansari et&#xa0;al., 2020</xref>; <xref ref-type="bibr" rid="B170">Paul et&#xa0;al., 2015</xref>; <xref ref-type="bibr" rid="B54">Constantin et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Polysaccharide NPs</td>
<td valign="top" align="left">Improved antimicrobial and antioxidant activity</td>
<td valign="top" align="left">Drug delivery</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B175">Qin et&#xa0;al., 2018</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Modified sodium montmorillonite</td>
<td valign="top" align="left">Corrosion resistance and hydrophobicity</td>
<td valign="top" align="left">Nanocomposites</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B208">Sheydaei et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. applanatum</italic>
</td>
<td valign="top" align="left">Silver (Ag-NPs)</td>
<td valign="top" align="left">Active vs. <italic>E. coli</italic> and <italic>S. aureus</italic>
</td>
<td valign="top" align="left">Biomedical applications</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B141">Mohanta et&#xa0;al., 2016</xref>; <xref ref-type="bibr" rid="B99">Jogaiah et&#xa0;al., 2019</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">
<italic>G. sessiliforme</italic>
</td>
<td valign="top" align="left">Silver (Ag-NPs)</td>
<td valign="top" align="left">Effective vs. foodborne pathogens</td>
<td valign="top" align="left">Antioxidant and cytotoxic effects</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B140">Mohanta et&#xa0;al., 2018</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Copper oxide (CuONPs)</td>
<td valign="top" align="left">Active vs. <italic>S. aureus</italic>, <italic>E. coli</italic>, and <italic>P. aeruginosa</italic>
</td>
<td valign="top" align="left">Treatment of superficial infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B78">Flores-R&#xe1;bago et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. sessile</italic>
</td>
<td valign="top" align="left">Metallic NPs</td>
<td valign="top" align="left">Active vs. <italic>Campylobacter jejuni</italic>
</td>
<td valign="top" align="left">Foodborne illness control</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B183">Rivera-Mendoza et&#xa0;al., 2024</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. resinaceum</italic>
</td>
<td valign="top" align="left">Silver (Ag-NPs)</td>
<td valign="top" align="left">Active vs. multidrug-resistant pathogens</td>
<td valign="top" align="left">&#x2014;</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B12">Ali Syed et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. boninense</italic>
</td>
<td valign="top" align="left">Phenolic compounds</td>
<td valign="top" align="left">Strong fungitoxicity</td>
<td valign="top" align="left">&#x2014;</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B50">Chong et&#xa0;al., 2011</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">
<italic>Ganoderma</italic> spp.</td>
<td valign="top" align="left">Titanium dioxide (TiO<sub>2</sub>) NPs</td>
<td valign="top" align="left">Effective vs. biofilm-forming pathogens</td>
<td valign="top" align="left">Clinical antibacterial agents</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B131">Marzhoseyni et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Silver nanocomplex</td>
<td valign="top" align="left">Broad-spectrum bactericidal</td>
<td valign="top" align="left">Eco-friendly antimicrobial agent</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B212">Shokouhi et&#xa0;al., 2023</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>In resource-limited settings where access to antibiotics is restricted, these green-synthesized nanoparticles offer a cost-effective and scalable antimicrobial alternative. Their ability to disrupt bacterial membranes, generate ROS, and inhibit efflux pumps suggests utility in treating persistent infections such as those found in tuberculosis, diabetic wounds, and catheter-associated UTIs (<xref ref-type="bibr" rid="B8">Al-Ansari et&#xa0;al., 2020</xref>; <xref ref-type="bibr" rid="B31">Bhardwaj et&#xa0;al., 2016</xref>). Moreover, the low toxicity of <italic>Ganoderma</italic>-synthesized copper oxide nanoparticles (CuONPs) supports their potential use in topical formulations for superficial infections, particularly in low-income regions (<xref ref-type="bibr" rid="B78">Flores-R&#xe1;bago et&#xa0;al., 2023</xref>).</p>
<p>Importantly, <italic>Ganoderma</italic>-derived nanoparticles also show activity against biofilm-forming pathogens, a major clinical challenge in implant-related infections and chronic wounds. Biofilms protect microbes from host immunity and antibiotics, contributing to prolonged hospital stays and increased mortality. Titanium dioxide nanoparticles combined with <italic>Ganoderma</italic> extracts have shown antibiofilm efficacy, which could be leveraged in medical device coatings and sterile wound dressings (<xref ref-type="bibr" rid="B131">Marzhoseyni et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B170">Paul et&#xa0;al., 2015</xref>). The anticancer and antioxidant properties of these nanoparticles add another layer of relevance. Ag-NPs synthesized from <italic>G. lucidum</italic> and <italic>G. sessiliforme</italic> have demonstrated cytotoxicity against breast and lung cancer cell lines, potentially addressing cancer-related infections and immune suppression (<xref ref-type="bibr" rid="B140">Mohanta et&#xa0;al., 2018</xref>; <xref ref-type="bibr" rid="B31">Bhardwaj et&#xa0;al., 2016</xref>). In cancer patients with neutropenia or post-chemotherapy immune suppression, fungal or bacterial co-infections are common. Thus, dual-action nanoparticles offer a novel approach to oncological support therapy.</p>
<p>In food safety and agriculture, <italic>Ganoderma</italic>-based nanoparticles have been tested against <italic>Campylobacter jejuni</italic>, a major cause of gastroenteritis and post-infectious sequelae in developing nations (<xref ref-type="bibr" rid="B183">Rivera-Mendoza et&#xa0;al., 2024</xref>). This points to a broader public health application, particularly in addressing foodborne diseases and improving sanitation in regions with limited access to refrigeration or clean water. Although current studies are predominantly <italic>in vitro</italic>, the eco-friendly synthesis, scalability, and multipotent biological activities of <italic>Ganoderma</italic>-derived nanoparticles position them as strong candidates for next-generation antimicrobials. Future work must address <italic>in vivo</italic> efficacy, targeted delivery mechanisms, pharmacokinetics, and regulatory considerations to facilitate clinical translation. Hence, <italic>Ganoderma</italic>-based nanomaterials not only show promise against MDR pathogens and biofilms but also align with global health priorities such as reducing AMR, treating co-infections in cancer or HIV patients, and improving access to antimicrobial materials in underserved regions. These properties highlight their unmet therapeutic potential in both developed and developing healthcare systems.</p>
</sec>
</sec>
<sec id="s5_2">
<label>5.2</label>
<title>Fungal infections</title>
<p>Fungal infections pose a growing threat to global health, particularly among immunocompromised individuals, transplant recipients, and patients undergoing chemotherapy. According to the Global Action Fund for Fungal Infections, over 1.5 million deaths annually are attributed to invasive fungal diseases, and current treatments are limited by toxicity, poor bioavailability, and rising resistance&#x2014;especially in <italic>Candida</italic> and <italic>Aspergillus</italic> species. The pipeline for new antifungal drugs remains dangerously sparse, underlining the urgent need for novel, safer, and more effective agents. Against this backdrop, <italic>Ganoderma</italic> species, particularly <italic>G. lucidum</italic>, offer promising antifungal potential with mechanisms distinct from conventional agents (<xref ref-type="table" rid="T6">
<bold>Table&#xa0;6</bold>
</xref>). <italic>G. lucidum</italic> has demonstrated broad-spectrum activity against pathogenic fungi, including <italic>C. albicans</italic>, <italic>Aspergillus flavus</italic>, and <italic>Fusarium oxysporum</italic>, with some studies reporting MIC values below 1 &#xb5;g/mL (<xref ref-type="bibr" rid="B35">Bitew and Abate, 1994</xref>). These findings are not merely academic; they suggest that <italic>Ganoderma</italic>-derived compounds could fill critical therapeutic gaps in treating drug-resistant candidiasis and aspergillosis, which are common and often fatal in ICU patients and those with hematological malignancies.</p>
<table-wrap id="T6" position="float">
<label>Table&#xa0;6</label>
<caption>
<p>Antifungal compounds and activities of various <italic>Ganoderma</italic> species against pathogenic fungi.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">Species</th>
<th valign="top" align="left">Antifungal compound</th>
<th valign="top" align="left">Target pathogen</th>
<th valign="top" align="left">Disease relevance/Target infection</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">Culture filtrate</td>
<td valign="top" align="left">
<italic>Candida albicans</italic>
</td>
<td valign="top" align="left">Candidiasis (oral, vaginal, and systemic)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B35">Bitew and Abate, 1994</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="10" align="left"/>
<td valign="top" align="left">Ganodermin</td>
<td valign="top" align="left">Plant and postharvest fungi</td>
<td valign="top" align="left">Agricultural applications (not animal/human-specific)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B236">Wang and Ng, 2006</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Toothpaste formulation</td>
<td valign="top" align="left">Oral <italic>Candida</italic>
</td>
<td valign="top" align="left">Oral candidiasis and dental hygiene</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B62">Dzubak et&#xa0;al., 2006</xref>; <xref ref-type="bibr" rid="B155">Nayak et&#xa0;al., 2010b</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Acetone extract</td>
<td valign="top" align="left">Filamentous fungi</td>
<td valign="top" align="left">Respiratory or skin mycoses</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B214">Singh et&#xa0;al., 2014</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Methanolic extracts</td>
<td valign="top" align="left">Soil and plant-associated fungi</td>
<td valign="top" align="left">Opportunistic infections in immunocompromised hosts</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B24">Baig et&#xa0;al., 2015</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Ethanol and aqueous extracts</td>
<td valign="top" align="left">Opportunistic and phytopathogenic fungi</td>
<td valign="top" align="left">Human fungal infections (skin, respiratory); some plant relevance</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B169">Parkash and Sharma, 2016</xref>; <xref ref-type="bibr" rid="B177">Radhika and Rajan, 2021</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Glucan sulfate (GS)</td>
<td valign="top" align="left">
<italic>Aspergillus</italic> spp.</td>
<td valign="top" align="left">Aspergillosis (pulmonary or systemic)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B239">Wan-Mohtar et&#xa0;al., 2017</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">PMMA modification</td>
<td valign="top" align="left">
<italic>Candida albicans</italic>
</td>
<td valign="top" align="left">Denture-related candidiasis</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B67">Enaba and El Gendi, 2022</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Triterpenoids</td>
<td valign="top" align="left">Dermatophytes and molds</td>
<td valign="top" align="left">Skin infections like ringworm and athlete&#x2019;s foot</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B241">Wasser, 2011</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Secondary metabolites</td>
<td valign="top" align="left">Docked with <italic>S. aureus</italic> protein targets</td>
<td valign="top" align="left">Suggests dual antibacterial/antifungal action, relevant for mixed infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B156">Nguyen et&#xa0;al., 2024</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Ethanolic extracts</td>
<td valign="top" align="left">
<italic>Aspergillus flavus</italic>
</td>
<td valign="top" align="left">Food spoilage fungi and risk of aflatoxicosis in animals</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B234">Vahdani et&#xa0;al., 2022</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. boninense</italic>
</td>
<td valign="top" align="left">Methanolic extracts</td>
<td valign="top" align="left">
<italic>Candida albicans</italic>
</td>
<td valign="top" align="left">Vulvovaginal and systemic candidiasis</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B58">Daruliza et&#xa0;al., 2012</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. annulare</italic>
</td>
<td valign="top" align="left">Applanoxidic acids A, C, and F</td>
<td valign="top" align="left">Dermatophytes</td>
<td valign="top" align="left">Human skin infections (tinea and athlete&#x2019;s foot)</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B218">Smania et&#xa0;al., 2003</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. mbrekobenum</italic>
</td>
<td valign="top" align="left">Mycelial plugs</td>
<td valign="top" align="left">Feed-contaminating fungi</td>
<td valign="top" align="left">Prevention of mycotoxicosis in livestock</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B65">El-Fallal et&#xa0;al., 2021</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>Ganoderma</italic> sp.</td>
<td valign="top" align="left">Crude exopolysaccharides</td>
<td valign="top" align="left">Mixed fungal species</td>
<td valign="top" align="left">General antifungal for clinical and food safety uses</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B59">Demir and Yama&#xe7;, 2008</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left"/>
<td valign="top" align="left">Various extracts</td>
<td valign="top" align="left">Multiple human and plant pathogens</td>
<td valign="top" align="left">Broad antifungal; relevant for dermatological and respiratory infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B136">Migahed et&#xa0;al., 2018</xref>; <xref ref-type="bibr" rid="B151">Naveenkumar et&#xa0;al., 2018</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Not specified</td>
<td valign="top" align="left">
<italic>Aspergillus niger</italic>
</td>
<td valign="top" align="left">Opportunistic pathogen in immunocompromised individuals</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B45">Chandrawanshi and Shukla, 2019</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Among the most notable bioactives is ganodermin, a protein isolated from <italic>G. lucidum</italic> that inhibits multiple phytopathogens (<xref ref-type="bibr" rid="B236">Wang and Ng, 2006</xref>), with potential for further development into topical antifungal formulations. In clinical contexts, <italic>G. lucidum</italic> has been incorporated into products like antifungal toothpaste and biomaterials such as polymethylmethacrylate (PMMA), where it enhanced mechanical performance while inhibiting <italic>C. albicans</italic> biofilm formation, a common cause of denture stomatitis (<xref ref-type="bibr" rid="B155">Nayak et&#xa0;al., 2010b</xref>; <xref ref-type="bibr" rid="B67">Enaba and El Gendi, 2022</xref>).</p>
<p>The unique mode of action of <italic>Ganoderma</italic>-derived triterpenoids&#x2014;targeting ergosterol to disrupt fungal membranes&#x2014;may offer an alternative to existing ergosterol-targeting drugs like amphotericin B but with lower toxicity (<xref ref-type="bibr" rid="B241">Wasser, 2011</xref>). In addition, these compounds have demonstrated the ability to interfere with biofilm formation and fungal cell wall synthesis, both of which are key contributors to antifungal resistance and treatment failure (<xref ref-type="bibr" rid="B44">Chan et&#xa0;al., 2013</xref>).</p>
<p>Importantly, <italic>Ganoderma</italic> extracts have shown efficacy against dermatophytes such as <italic>Microsporum canis</italic> and <italic>Trichophyton mentagrophytes</italic>, which are prevalent in tropical climates and often undertreated due to limited healthcare access (<xref ref-type="bibr" rid="B218">Smania et&#xa0;al., 2003</xref>). In veterinary and agricultural sectors, <italic>Ganoderma</italic> is also emerging as a natural antifungal for contaminated feed and crops, suggesting a One Health approach to fungal control (<xref ref-type="bibr" rid="B65">El-Fallal et&#xa0;al., 2021</xref>). From a pharmaceutical development perspective, molecular docking studies have revealed strong binding affinities of <italic>Ganoderma</italic> metabolites to key fungal protein targets, offering a rational basis for structure-based drug design (<xref ref-type="bibr" rid="B156">Nguyen et&#xa0;al., 2024</xref>). This computational insight strengthens the argument for clinical translation and underscores the need for further <italic>in vivo</italic> validation and toxicity profiling. Hence, the antifungal properties of <italic>Ganoderma</italic> are not just promising <italic>in vitro</italic> but potentially transformative in clinical settings where fungal infections are increasing and treatment options remain inadequate. By targeting resistant strains, disrupting biofilms, and offering low-toxicity alternatives, <italic>Ganoderma</italic>-derived compounds could represent the next generation of antifungal therapeutics&#x2014;especially in settings where conventional options fall short.</p>
</sec>
<sec id="s5_3">
<label>5.3</label>
<title>Viral infections</title>
<p>Viral infections remain a major global health challenge, with diseases such as HIV/AIDS, hepatitis B (HBV), herpes simplex (HSV), and influenza collectively causing significant morbidity and mortality. According to UNAIDS, approximately 39 million people were living with HIV globally in 2023, while WHO reports over 250 million people chronically infected with HBV. These figures underscore the urgent need for novel antiviral agents, especially in light of emerging drug resistance and the limited efficacy or accessibility of current therapeutics in many regions. <italic>Ganoderma</italic> species, particularly <italic>G. lucidum</italic>, have garnered interest for their potential to address these unmet needs through their diverse arsenal of bioactive compounds (<xref ref-type="table" rid="T7">
<bold>Table&#xa0;7</bold>
</xref>). Isolated triterpenoids, such as ganoderic acid-&#x3b2;, lucidumol B, and ganodermanontriol, have demonstrated significant anti-HIV-1 protease activity, with IC<sub>50</sub> values ranging from 20 to 90 &#x3bc;M (<xref ref-type="bibr" rid="B137">Min et&#xa0;al., 1998</xref>; <xref ref-type="bibr" rid="B66">El-Mekkawy et&#xa0;al., 1998</xref>). Importantly, molecular docking studies suggest that ganoderic acid-B exhibits a binding affinity surpassing that of the standard drug nelfinavir, supporting its potential as a lead compound for drug development (<xref ref-type="bibr" rid="B104">Kang et&#xa0;al., 2015</xref>). In addition, enzymatic crude extracts rich in laccase from <italic>G. lucidum</italic> have shown remarkable <italic>in vitro</italic> inhibition of HIV-1 replication (<xref ref-type="bibr" rid="B250">Zhang et&#xa0;al., 2011</xref>; <xref ref-type="bibr" rid="B79">Fl&#xf3;rez-Sampedro et&#xa0;al., 2016</xref>), providing an alternative strategy targeting reverse transcription pathways.</p>
<table-wrap id="T7" position="float">
<label>Table&#xa0;7</label>
<caption>
<p>Antiviral activity of compounds derived from <italic>Ganoderma</italic> species against various viral infections.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">
<italic>Ganoderma</italic> species</th>
<th valign="top" align="left">Active compound(s)</th>
<th valign="top" align="left">Target virus</th>
<th valign="top" align="left">Mechanism/Effect</th>
<th valign="top" align="left">Disease relevance</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" rowspan="12" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">Ganoderic acid-&#x3b2;, lucidumol B, ganodermanondiol, ganodermanontriol, and ganolucidic acid A</td>
<td valign="top" align="left">HIV-1</td>
<td valign="top" align="left">Inhibits HIV-1 protease</td>
<td valign="top" align="left">Key for antiretroviral therapy; useful against AIDS</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B137">Min et&#xa0;al., 1998</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Ganoderic acid-&#x3b1;, ganoderiol F, and ganodermanontriol</td>
<td valign="top" align="left">HIV-1</td>
<td valign="top" align="left">Moderate inhibition of viral replication</td>
<td valign="top" align="left">May reduce HIV viral load in early stages</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B66">El-Mekkawy et&#xa0;al., 1998</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Triterpenoids and polysaccharides</td>
<td valign="top" align="left">HSV</td>
<td valign="top" align="left">Blocks viral entry</td>
<td valign="top" align="left">Potential for cold sore and genital herpes treatment</td>
<td valign="top" align="left">
</td>
</tr>
<tr>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">Influenza virus</td>
<td valign="top" align="left">Enhances host immune response</td>
<td valign="top" align="left">Immunostimulant for seasonal influenza</td>
<td valign="top" align="left">Li et&#xa0;al., 2015</td>
</tr>
<tr>
<td valign="top" align="left">Laccases</td>
<td valign="top" align="left">HIV-1</td>
<td valign="top" align="left">Inhibits reverse transcriptase</td>
<td valign="top" align="left">Possible treatment option for resistant HIV strains</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B250">Zhang et&#xa0;al., 2011</xref>; <xref ref-type="bibr" rid="B79">Fl&#xf3;rez-Sampedro et&#xa0;al., 2016</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Polysaccharides</td>
<td valign="top" align="left">HBV</td>
<td valign="top" align="left">Inhibits viral replication</td>
<td valign="top" align="left">May support chronic hepatitis B management</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B82">Gao et&#xa0;al., 2003</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Ganoderone C, lucialdehyde B, ergosta-7,22-dien-3&#x3b1;-ol</td>
<td valign="top" align="left">Influenza virus</td>
<td valign="top" align="left">Suppresses viral growth</td>
<td valign="top" align="left">Reduces severity and duration of flu symptoms</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B158">Niedermeyer et&#xa0;al., 2005</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Lanosta-trienone (GLTA) and ganoderic acid Y</td>
<td valign="top" align="left">Enterovirus 71</td>
<td valign="top" align="left">RNA replication inhibitor</td>
<td valign="top" align="left">Effective for hand-foot-and-mouth disease in children</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B251">Zhang et&#xa0;al., 2014</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Ganoderic acids A&#x2013;C1, H, and GS-2</td>
<td valign="top" align="left">HIV</td>
<td valign="top" align="left">Broad protease inhibition</td>
<td valign="top" align="left">Potential backbone compounds for HIV therapy</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B104">Kang et&#xa0;al., 2015</xref>; <xref ref-type="bibr" rid="B38">Cai et&#xa0;al., 2020</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Proteoglycan</td>
<td valign="top" align="left">HSV-1 and HSV-2</td>
<td valign="top" align="left">Pre- and co-treatment inhibition</td>
<td valign="top" align="left">Suitable for both prophylaxis and treatment of herpes</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B126">Liu et&#xa0;al., 2014</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Ganoderic acid H</td>
<td valign="top" align="left">HBV</td>
<td valign="top" align="left">Suppresses surface antigen expression</td>
<td valign="top" align="left">Relevant to controlling chronic hepatitis progression</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B120">Li and Wang, 2006</xref>; <xref ref-type="bibr" rid="B118">Kumar et&#xa0;al., 2020</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Hesperetin, ganosin B</td>
<td valign="top" align="left">Dengue virus</td>
<td valign="top" align="left">Inhibits viral protease</td>
<td valign="top" align="left">Promising approach to limit dengue replication</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B123">Lim et&#xa0;al., 2020</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. adspersum</italic>
</td>
<td valign="top" align="left">Crude extract</td>
<td valign="top" align="left">HSV-1</td>
<td valign="top" align="left">Broad-spectrum antiviral activity</td>
<td valign="top" align="left">Topical applications for recurrent herpes infections</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B247">Zahmoul et&#xa0;al., 2024</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. sinense</italic>
</td>
<td valign="top" align="left">Ganoderiol F, ganoderic acid GS-2, and lucidenic acids</td>
<td valign="top" align="left">HIV-1</td>
<td valign="top" align="left">High-affinity viral inhibition</td>
<td valign="top" align="left">May complement standard HIV therapeutics</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B64">El Dine et&#xa0;al., 2008</xref>; <xref ref-type="bibr" rid="B193">Sato et&#xa0;al., 2009</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. colossum</italic>
</td>
<td valign="top" align="left">Farnesyl hydroquinone, ganomycin I and B</td>
<td valign="top" align="left">HIV-1</td>
<td valign="top" align="left">Competitive inhibition of protease</td>
<td valign="top" align="left">Novel anti-HIV leads for drug development</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B64">El Dine et&#xa0;al., 2008</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. lingzhi</italic>
</td>
<td valign="top" align="left">Ganoderic TR and T-Q</td>
<td valign="top" align="left">H1N1 and H5N1</td>
<td valign="top" align="left">Neuraminidase inhibition</td>
<td valign="top" align="left">Potential therapy for influenza pandemics</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B256">Zhu et&#xa0;al., 2015</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. pfeifferi</italic>
</td>
<td valign="top" align="left">Ganodermadiol, lucidadiol, and applanoxidic acid G</td>
<td valign="top" align="left">Influenza A</td>
<td valign="top" align="left">Moderate suppression of viral activity</td>
<td valign="top" align="left">May assist in reducing viral load during flu outbreaks</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B145">Mothana et&#xa0;al., 2003</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>The antiviral effects of <italic>Ganoderma</italic> extend beyond HIV. Polysaccharides and triterpenes from <italic>G. lucidum</italic> have shown inhibitory activity against HSV and influenza virus. These effects are attributed to both direct interference with viral entry and replication, as well as enhancement of host immunity through cytokine stimulation (<xref ref-type="bibr" rid="B28">Basnet et&#xa0;al., 2017</xref>). This dual mode of action is particularly relevant in immunocompromised populations where traditional antivirals may fail or cause adverse effects. Notably, <italic>Ganoderma adspersum</italic> extract demonstrated potent activity against HSV-1 with a high selective index and protective efficacy (<xref ref-type="bibr" rid="B247">Zahmoul et&#xa0;al., 2024</xref>), highlighting its therapeutic potential for dermatological or mucosal viral infections. Furthermore, triterpenoids such as ganoderiol F, ganodermadiol, and colossolactones isolated from <italic>G. lucidum</italic>, <italic>G. sinense</italic>, and <italic>G. colossum</italic> have shown broad-spectrum activity against HIV-1, HSV, and influenza viruses with IC<sub>50</sub> or ED<sub>50</sub> values within pharmacologically relevant ranges (<xref ref-type="bibr" rid="B64">El Dine et&#xa0;al., 2008</xref>; <xref ref-type="bibr" rid="B193">Sato et&#xa0;al., 2009</xref>; <xref ref-type="bibr" rid="B145">Mothana et&#xa0;al., 2003</xref>). These findings suggest that <italic>Ganoderma</italic> may serve as a platform for developing multitarget antivirals&#x2014;particularly valuable in resource-limited settings where polyvalent therapies are needed to treat co-infections. Although current evidence is largely preclinical, these studies collectively position <italic>Ganoderma</italic>-derived compounds as promising candidates for addressing therapeutic gaps in managing persistent and drug-resistant viral infections. Future efforts should focus on validating these compounds in clinical models and elucidating their pharmacokinetics and immunomodulatory effects to advance their development into viable antiviral therapies.</p>
</sec>
<sec id="s5_4">
<label>5.4</label>
<title>Parasitic infections</title>
<p>Parasitic diseases continue to exact a significant toll on global health, particularly in tropical and subtropical regions. Malaria alone caused over 600,000 deaths in 2022, predominantly among children under five in sub-Saharan Africa (<xref ref-type="bibr" rid="B243">World Health Organization, 2024</xref>). Other parasitic infections, such as toxoplasmosis, giardiasis, leishmaniasis, and blastocystosis, also contribute to considerable morbidity, with limited treatment options, increasing drug resistance, and toxicity issues posing substantial therapeutic challenges. Recent research has highlighted the potential antiparasitic properties of <italic>Ganoderma</italic> species, revealing promising efficacy against several protozoal and parasitic infections (<xref ref-type="table" rid="T8">
<bold>Table&#xa0;8</bold>
</xref>). Notably, nortriterpenes ganoboninketals A&#x2013;C, derived from <italic>G. boninense</italic> fruiting bodies, demonstrated potent antiplasmodial activity against <italic>Plasmodium falciparum</italic> with IC<sub>50</sub> values of 4.0, 7.9, and 1.7 &#x3bc;M, respectively (<xref ref-type="bibr" rid="B4">Adams et&#xa0;al., 2010</xref>; <xref ref-type="bibr" rid="B129">Ma et&#xa0;al., 2014</xref>; <xref ref-type="fig" rid="f2">
<bold>Figure 2</bold>
</xref>). Additional triterpenes&#x2014;schisanlactone B, ganodermalactone F, and colossolactone E&#x2014;isolated from <italic>Ganoderma</italic> sp. KM01 also showed activity against <italic>P. falciparum</italic>, with IC<sub>50</sub> values ranging from 6.0 to 10.0 &#x3bc;M (<xref ref-type="bibr" rid="B119">Lakornwong et&#xa0;al., 2014</xref>). Moreover, <italic>G. lucidum</italic>-derived compounds such as ganoderic acids (DM, TR1, and S), ganodermanondiol, and ganofuran B, isolated using EtOAc, exhibited inhibitory effects on <italic>P. falciparum</italic> within a 6.0&#x2013;20 &#x3bc;M IC<sub>50</sub> range (<xref ref-type="bibr" rid="B4">Adams et&#xa0;al., 2010</xref>). These activities fall within a biologically relevant range, highlighting their potential as lead compounds for the development of novel antimalarials, especially in the face of rising resistance to artemisinin-based therapies.</p>
<table-wrap id="T8" position="float">
<label>Table&#xa0;8</label>
<caption>
<p>Antiparasitic properties of <italic>Ganoderma</italic> species.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">
<italic>Ganoderma</italic> species</th>
<th valign="top" align="left">Active compounds/extracts</th>
<th valign="top" align="left">Target parasite</th>
<th valign="top" align="left">Disease relevance/Efficacy</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">
<italic>G. boninense</italic>
</td>
<td valign="top" align="left">Ganoboninketals A&#x2013;C</td>
<td valign="top" align="left">
<italic>Plasmodium falciparum</italic>
</td>
<td valign="top" align="left">Exhibits strong antiplasmodial activity; promising for malaria drug development</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B4">Adams et&#xa0;al., 2010</xref>; <xref ref-type="bibr" rid="B129">Ma et&#xa0;al., 2014</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">Ganoderic acids (DM, TR1, and S), ganodermanondiol, and ganofuran B</td>
<td valign="top" align="left">Targets plasmepsin I enzyme in <italic>Plasmodium</italic>
</td>
<td valign="top" align="left">Inhibits a key enzyme in malaria parasite; potential antimalarial candidates</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B4">Adams et&#xa0;al., 2010</xref>; <xref ref-type="bibr" rid="B104">Kang et&#xa0;al., 2015</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Hydroalcoholic extract</td>
<td valign="top" align="left">
<italic>Toxoplasma gondii</italic> (RH strain)</td>
<td valign="top" align="left">More effective than aqueous and alcoholic extracts; potential toxoplasmosis treatment</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B7">Ahmadi et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="2" align="left">
<italic>Ganoderma</italic> spp.</td>
<td valign="top" align="left">Lectins</td>
<td valign="top" align="left">
<italic>Heterodera glycines</italic> and <italic>Ditylenchus dipsaci</italic> (plant-parasitic nematodes)</td>
<td valign="top" align="left">Limited antiparasitic effect; not viable for agricultural use</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B253">Zhao et&#xa0;al., 2009</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">Crude extract</td>
<td valign="top" align="left">
<italic>Blastocystis hominis</italic>
</td>
<td valign="top" align="left">Inhibits growth and induces morphological damage; potential for protozoal infection management</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B101">Kaewjai et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B233">Uwidia et&#xa0;al., 2024</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>Ganoderma</italic> sp. KM01</td>
<td valign="top" align="left">Schisanlactone B, ganodermalactone F, and colossolactone E</td>
<td valign="top" align="left">
<italic>Plasmodium falciparum</italic>
</td>
<td valign="top" align="left">Moderate inhibition; candidates for further antimalarial screening</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B119">Lakornwong et&#xa0;al., 2014</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>In studies on nematode inhibition, <xref ref-type="bibr" rid="B253">Zhao et&#xa0;al. (2009)</xref> reported that lectins from <italic>Ganoderma</italic> exhibited activity against plant nematodes <italic>Heterodera glycines</italic> and <italic>Ditylenchus dipsaci</italic>, although their potency was deemed insufficient for practical use. Nonetheless, these findings provide a foundation for future optimization or bioengineering approaches to enhance antihelminthic efficacy. Computational studies further support the antiparasitic potential of <italic>Ganoderma</italic> compounds. <italic>G. lucidum</italic> triterpenoids were shown to interact with plasmepsin I, a key enzyme in <italic>P. falciparum</italic>. Ganodermanondiol demonstrated the highest affinity (binding energy = &#x2212;7.14 kcal/mol, <italic>K</italic>
<sub>i</sub> = 0.005 mM), outperforming the standard inhibitor KNI-10006 (<xref ref-type="bibr" rid="B104">Kang et&#xa0;al., 2015</xref>). This suggests a plausible mechanism of action and reinforces the value of <italic>Ganoderma</italic> constituents in rational drug design against malaria. <italic>Ganoderma</italic> extracts also displayed antiprotozoal effects against <italic>Blastocystis hominis</italic>, a parasite increasingly associated with gastrointestinal disorders. Strong inhibitory activity was observed at an MIC of 62.5 &#x3bc;g/mL. At higher concentrations, extracts of <italic>Ganoderma</italic> and <italic>Boesenbergia rotunda</italic> reduced <italic>B. hominis</italic> growth by up to 90% within 12 h and induced notable morphological damage, pointing to their potential in managing treatment-refractory blastocystosis (<xref ref-type="bibr" rid="B101">Kaewjai et&#xa0;al., 2023</xref>; <xref ref-type="bibr" rid="B233">Uwidia et&#xa0;al., 2024</xref>). In addition, <italic>G. lucidum</italic> extracts demonstrated anti-<italic>Toxoplasma</italic> effects, particularly against <italic>Toxoplasma gondii</italic> RH strain tachyzoites. <italic>In vitro</italic> studies showed that the hydroalcoholic extract of <italic>G. lucidum</italic> exhibited the highest toxoplasmacidal activity and selectivity (EC<sub>50</sub> = 3.274), outperforming both aqueous (EC<sub>50</sub>: 76.32) and alcoholic extracts (EC<sub>50</sub>: 40.18) (<xref ref-type="bibr" rid="B7">Ahmadi et&#xa0;al., 2023</xref>). Given the limited efficacy and potential teratogenicity of current anti-toxoplasmosis treatments, such natural alternatives may offer safer and more accessible interventions, especially in immunocompromised populations. Overall, these findings suggest that <italic>Ganoderma</italic>-derived metabolites hold considerable promise in addressing parasitic diseases where conventional therapies fall short. Future studies should aim to evaluate their efficacy <italic>in vivo</italic>, explore their mechanisms of action, and assess safety profiles to support clinical translation.</p>
</sec>
</sec>
<sec id="s6">
<label>6</label>
<title>Clinical studies on antimicrobial properties of <italic>Ganoderma</italic>
</title>
<p>
<italic>G. lucidum</italic> has been extensively studied for its antimicrobial properties, particularly in laboratory and animal models. <italic>In vitro</italic> studies have demonstrated that its bioactive compounds&#x2014;mainly polysaccharides and triterpenoids&#x2014;possess antiviral, antibacterial, and antifungal activities. Despite these promising findings, human clinical evidence remains limited, with most clinical research to date focusing on immune modulation, cancer therapy, and liver protection rather than direct antimicrobial effects. Some preliminary clinical studies suggest potential antiviral benefits. A pilot clinical trial conducted by <xref ref-type="bibr" rid="B91">Hijikata et&#xa0;al. (2005)</xref> evaluated an herbal formula containing <italic>G. lucidum</italic> in patients with herpes zoster (shingles). Participants who received 750 mg daily experienced rapid symptom relief, with most resolving within 10 days, and no cases of postherpetic neuralgia were reported after 1 year. In a subsequent study by the same group (<xref ref-type="bibr" rid="B90">Hijikata et&#xa0;al., 2007</xref>), individuals with recurrent herpes simplex infections who were treated with a hot water extract of <italic>G. lucidum</italic> at 4 g daily reported faster symptom resolution&#x2014;genital herpes symptoms improved in 4.9 &#xb1; 1.3 days compared to 10.9 &#xb1; 6.3 days without treatment. However, both studies involved combination herbal formulas, making it difficult to isolate the specific effects of <italic>G. lucidum</italic>. To date, there are no human clinical trials specifically evaluating the antibacterial efficacy of <italic>G. lucidum</italic>, and evidence in this area is limited to <italic>in vitro</italic> findings. Similarly, while antifungal activity has been reported in laboratory settings&#x2014;particularly against <italic>Candida</italic> species and dermatophytes&#x2014;no human studies have validated these effects clinically. Research on its antiparasitic activity remains scarce, with neither significant preclinical nor clinical data currently available.</p>
</sec>
<sec id="s7">
<label>7</label>
<title>
<italic>Ganoderma</italic> against plant pathogens</title>
<p>Research on <italic>Ganoderma</italic> has revealed its potential as a natural biocontrol agent against various plant pathogens. Numerous studies have documented its antimicrobial effects, highlighting its capacity to combat fungal and bacterial infections in plants. <italic>G. lucidum</italic> mycelia showed moderate antimicrobial activity against soil-borne pathogens, including fungi (<italic>F. oxysporum</italic>, <italic>Rhizoctonia solani</italic>, and <italic>Sclerotium rolfsii</italic>) and bacteria (<italic>R. solanacearum</italic> and <italic>S. aureus</italic>). <italic>In vitro</italic>, mycelial extracts increased inhibition zones, while <italic>in vivo</italic> tests on tomato seedlings delayed disease symptoms, suggesting <italic>G. lucidum</italic> as a potential biocontrol agent, particularly against <italic>R. solani</italic> and <italic>S. rolfsii</italic> (<xref ref-type="bibr" rid="B135">Mendoza and Nepomuceno, 2006</xref>). <italic>G. lucidum</italic> extracts exhibit antifungal properties effective against plant pathogens <italic>F. oxysporum</italic> and <italic>Alternaria alternata</italic> in marigolds. This study compared organic and aqueous extracts of <italic>G. lucidum</italic>, applying various concentrations (5%, 10%, 15%, and 20%) using Agar absorption, Agar well diffusion, and Vapor assay methods. Methanolic extract showed the highest inhibition (64%) using the Agar absorption method, while aqueous extract showed the lowest inhibition (38%) with Agar well diffusion. These findings highlight the potential of <italic>G. lucidum</italic> methanolic extract as a biological control agent for marigold plant diseases (<xref ref-type="bibr" rid="B200">Shahid et&#xa0;al., 2016</xref>). The antimicrobial activity of extracts from wood-rotting Basidiomycetes mushrooms from <italic>Eucalyptus</italic> plantations in Uruguay was investigated. Eight extracts, including those from <italic>G. resinaceum</italic> and <italic>L. sulphureus</italic>, were active against pathogens such as <italic>Xanthomonas vesicatoria</italic> and <italic>Aspergillus oryzae</italic> (<xref ref-type="bibr" rid="B26">Barneche et&#xa0;al., 2016</xref>). A compound named G_app7, isolated from <italic>G. applanatum</italic>, was found to effectively inhibit the growth of <italic>Sclerospora graminicola</italic>, the pathogen causing downy mildew in pearl millet (<italic>Pennisetum glaucum</italic>). G_app7 reduced sporangium formation (41.4%), zoospore release (77.5%), and motility (91%), and closely resembles metominostrobin, a fungicide. It remained effective at temperatures between 25 and 80&#xb0;C and was stable for at least 12 months at 4&#xb0;C. Seed treatment with G_app7 provided a 63% increase in disease protection compared to controls, highlighting its potential as an environmentally safe agrochemical for pearl millet protection (<xref ref-type="bibr" rid="B100">Jogaiah et&#xa0;al., 2016</xref>).</p>
<p>The antibacterial effects of selenium-containing biocomposites from submerged cultures of <italic>Ganoderma</italic> species were studied against plant pathogenic bacteria. Biocomposites from <italic>G. cattienensis</italic> and <italic>G. lucidum</italic> were most effective against <italic>C. michiganensis</italic>, while those from <italic>G. valesiacum</italic> and <italic>G. lucidum</italic> showed strong activity against <italic>Xanthomonas campestris</italic>. <italic>G. colossus</italic> exhibited notable activity against <italic>Pseudomonas fluorescens</italic>. The study highlights the potential of using coumarin-based compounds for producing antimicrobial substances from fungi (<xref ref-type="bibr" rid="B171">Perfileva et&#xa0;al., 2017</xref>). Eight mushroom species were screened, including <italic>G. lucidum</italic>, for their impact on <italic>Colletotrichum capsici</italic>, the chili fruit rot pathogen. The results revealed that <italic>G. lucidum</italic>, <italic>Auricularia polytricha</italic>, and <italic>Lentinus edodes</italic> demonstrated significant antifungal activity, with <italic>G. lucidum</italic> achieving the highest mycelial growth inhibition (54.81%). Chloroform extracts from <italic>G. lucidum</italic> inhibited spore germination (88%) and mycelial growth (60.55%) at 24 h. These findings suggest <italic>G. lucidum</italic> as a promising source for developing fungicides against <italic>C. capsici</italic>, warranting further investigation of its active compounds (<xref ref-type="bibr" rid="B173">Priy et&#xa0;al., 2019</xref>).</p>
<p>The antimicrobial potential of an aqueous ammonia extract from <italic>G. lucidum</italic> carpophores, sourced from <italic>Quercus ilex</italic> trees, was investigated, revealing key chemical constituents such as acetamide and oleic acid. The extract exhibited strong anti-oomycete and antifungal activities, with MIC values of 187.5 &#x3bc;g&#xb7;mL<sup>&#x2212;1</sup> against <italic>Phytophthora cinnamomi</italic> and varying MICs against other fungi. When conjugated with chitosan oligomers, the extract&#x2019;s antimicrobial efficacy significantly increased, showcasing MIC values as low as 78.12 &#x3bc;g&#xb7;mL<sup>&#x2212;1</sup>, demonstrating its potential for protecting holm oak in sustainable agricultural practices (<xref ref-type="bibr" rid="B189">S&#xe1;nchez-Hern&#xe1;ndez et&#xa0;al., 2023</xref>). The antifungal properties of <italic>G. lucidum</italic> against the mango anthracnose pathogen <italic>C. gloeosporioides</italic> were investigated in this study. Ethyl acetate extracts from the fruiting body inhibited mycelial growth by 70.10% at a 1% concentration. Thin-layer chromatography identified two active bands, with the first achieving 53.77% inhibition. Gas chromatography&#x2013;mass spectrometry detected benzothiazole, which completely inhibited mycelial growth at 50 ppm and caused structural abnormalities in the pathogen. The findings suggest that <italic>G. lucidum</italic> biomolecules could be effective natural agents against plant pathogens (<xref ref-type="bibr" rid="B148">Muniyappan et&#xa0;al., 2023</xref>). The crude extract of <italic>G. lucidum</italic> was formulated into an emulsion [water in oil (W/O)] to induce systemic resistance in chickpeas against <italic>Fusarium</italic> wilt caused by <italic>F. oxysporum</italic> f. sp. <italic>ciceri</italic> (FOC). Different dilutions of the formulation were applied to chickpeas, which were then challenged with FOC. Enzyme assays showed increased activity of peroxidase (PO), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL) in treated plants, indicating activation of the plant&#x2019;s natural defense pathways. GC-MS analysis confirmed bioactive compounds responsible for enhancing enzyme levels. This study suggests the potential for developing bio-formulations to control plant diseases (<xref ref-type="bibr" rid="B215">Singh and Vyas, 2023</xref>). <xref ref-type="table" rid="T9">
<bold>Table&#xa0;9</bold>
</xref> summarizes the antimicrobial activities of <italic>Ganoderma</italic> species against plant pathogens.</p>
<table-wrap id="T9" position="float">
<label>Table&#xa0;9</label>
<caption>
<p>Antimicrobial activity of <italic>Ganoderma</italic> spp. against plant pathogens.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="left">
<italic>Ganoderma</italic> species</th>
<th valign="top" align="left">Target pathogen(s)</th>
<th valign="top" align="left">Type of activity</th>
<th valign="top" align="left">Key findings</th>
<th valign="top" align="left">Disease relevance</th>
<th valign="top" align="left">References</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">
<italic>G. applanatum</italic>
</td>
<td valign="top" align="left">
<italic>Sclerospora graminicola</italic> (pearl millet downy mildew)</td>
<td valign="top" align="left">Antifungal <italic>(in vitro</italic>)</td>
<td valign="top" align="left">Isolate G_app7 suppressed spore formation and improved plant resistance</td>
<td valign="top" align="left">Potential bioagent for downy mildew control in cereals</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B100">Jogaiah et&#xa0;al., 2016</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. cattienensis</italic> and <italic>G. lucidum</italic>
</td>
<td valign="top" align="left">
<italic>Clavibacter michiganensis</italic>, <italic>X. campestris</italic>, and <italic>P. fluorescens</italic>
</td>
<td valign="top" align="left">Antibacterial (selenium biocomposites)</td>
<td valign="top" align="left">Selenium nanoparticles from Ganoderma selectively inhibited bacterial growth</td>
<td valign="top" align="left">Useful for agricultural pathogen control and seed coating</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B171">Perfileva et&#xa0;al., 2017</xref>
</td>
</tr>
<tr>
<td valign="top" rowspan="6" align="left">
<italic>G. lucidum</italic>
</td>
<td valign="top" align="left">
<italic>Phytophthora cinnamomi</italic> and other phytopathogens</td>
<td valign="top" align="left">Antifungal and anti-oomycete</td>
<td valign="top" align="left">Efficacy enhanced by chitosan combination</td>
<td valign="top" align="left">Effective against root rot and damping-off diseases</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B189">S&#xe1;nchez-Hern&#xe1;ndez et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>Fusarium oxysporum</italic> f. sp. <italic>ciceri</italic> (chickpea wilt)</td>
<td valign="top" align="left">Induced systemic resistance</td>
<td valign="top" align="left">Stimulated plant defense enzymes (PO, PPO, and PAL)</td>
<td valign="top" align="left">Sustainable control of <italic>Fusarium</italic> wilt in legumes</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B215">Singh and Vyas, 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>Colletotrichum gloeosporioides</italic> (mango anthracnose)</td>
<td valign="top" align="left">Antifungal (<italic>in vitro</italic>)</td>
<td valign="top" align="left">70% inhibition of mycelial growth; benzothiazole identified</td>
<td valign="top" align="left">Potential for pre-harvest mango protection</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B148">Muniyappan et&#xa0;al., 2023</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>F. oxysporum</italic>, <italic>R. solani</italic>, <italic>S. rolfsii</italic>, and <italic>R. solanacearum</italic>
</td>
<td valign="top" align="left">Antifungal, antibacterial (<italic>in vitro</italic> and <italic>in vivo</italic>)</td>
<td valign="top" align="left">Mycelial extract delayed disease onset and increased inhibition zones</td>
<td valign="top" align="left">Broad-spectrum plant disease control</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B135">Mendoza and Nepomuceno, 2006</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>F. oxysporum</italic> and <italic>Alternaria alternata</italic> (marigold pathogens)</td>
<td valign="top" align="left">Antifungal (<italic>in vitro</italic>)</td>
<td valign="top" align="left">Methanolic extract had 64% growth inhibition</td>
<td valign="top" align="left">Alternative to chemical fungicides for ornamentals</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B200">Shahid et&#xa0;al., 2016</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>Colletotrichum capsici</italic> (chili fruit rot)</td>
<td valign="top" align="left">Antifungal (<italic>in vitro</italic>)</td>
<td valign="top" align="left">Inhibited spore germination (88%) and mycelial growth (54.8%)</td>
<td valign="top" align="left">Biocontrol option for chili postharvest spoilage</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B173">Priy et&#xa0;al., 2019</xref>
</td>
</tr>
<tr>
<td valign="top" align="left">
<italic>G. resinaceum</italic> and <italic>Laetiporus sulphureus</italic>
</td>
<td valign="top" align="left">
<italic>X. vesicatoria</italic> and <italic>Aspergillus oryzae</italic>
</td>
<td valign="top" align="left">Antibacterial and antifungal (<italic>in vitro</italic>)</td>
<td valign="top" align="left">Crude extracts suppressed growth of pathogens from <italic>Eucalyptus</italic> plantations</td>
<td valign="top" align="left">Supports integrated pest management in forestry</td>
<td valign="top" align="left">
<xref ref-type="bibr" rid="B26">Barneche et&#xa0;al., 2016</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s8">
<label>8</label>
<title>Challenges and limitations of <italic>Ganoderma</italic> in antimicrobial applications</title>
<p>Although <italic>Ganoderma</italic>, especially <italic>G. lucidum</italic>, has demonstrated promising antimicrobial properties, several key challenges limit its broader adoption in medical and agricultural settings. These challenges primarily stem from variability in species, inconsistency in extract composition, and a lack of robust human clinical research specifically targeting antimicrobial use. A major hurdle is the natural variation in bioactive compounds among different <italic>Ganoderma</italic> species. Each species produces a unique blend of compounds&#x2014;such as polysaccharides, triterpenoids, and phenolics&#x2014;which directly influences their antimicrobial efficacy. Even within the same species, factors like geographical origin, climate, substrate, and cultivation conditions can alter the concentration and types of active molecules. This variability makes it difficult to predict or compare the antimicrobial strength of different extracts, reducing their reliability as standardized treatments. Another significant limitation lies in the difficulty of standardizing <italic>Ganoderma</italic> extracts. Unlike conventional pharmaceuticals that are based on single, well-defined molecules, <italic>Ganoderma</italic> extracts are complex mixtures. Depending on the extraction method used&#x2014;whether water-based or alcohol-based&#x2014;the resulting compounds and their concentrations can vary greatly. This leads to inconsistent therapeutic profiles, making dosage optimization and reproducibility a challenge. Furthermore, there is currently no universally accepted quality control standard for <italic>Ganoderma</italic> products, which adds another layer of uncertainty for clinical or commercial use. Perhaps the most critical limitation is the lack of extensive human clinical trials specifically designed to assess antimicrobial effects of <italic>Ganoderma</italic>. While laboratory and animal studies have shown promising results against bacteria, fungi, and viruses, human trials remain scarce. Most clinical research has focused on immune modulation, cancer support, and liver protection, rather than on infectious diseases. Without rigorous clinical testing, questions remain about its safety, appropriate dosing, and real-world efficacy. This lack of data also presents a barrier to regulatory approval and mainstream medical acceptance, hindering the development of <italic>Ganoderma</italic>-based antimicrobial therapies. Although <italic>Ganoderma</italic> holds great promise as a natural antimicrobial agent, issues related to species variability, extract standardization, and insufficient clinical evidence must be addressed before it can be reliably integrated into therapeutic or agricultural practices.</p>
</sec>
<sec id="s9">
<label>9</label>
<title>Future research directions for <italic>Ganoderma</italic> in antimicrobial applications</title>
<p>The growing recognition of antimicrobial properties of <italic>Ganoderma</italic> highlights several critical research avenues that could unlock its full therapeutic potential. First and foremost, standardizing <italic>Ganoderma</italic> extracts is essential to ensure consistency in their bioactive compounds, such as polysaccharides, triterpenoids, and phenolics. Variations in species, cultivation methods, and extraction techniques currently lead to unpredictable antimicrobial effects, limiting reproducibility in both research and clinical applications. Future studies should focus on optimizing extraction protocols and determining minimum effective concentrations to create reliable, high-quality formulations suitable for pharmaceutical use. Another promising direction involves developing <italic>Ganoderma</italic>-based antimicrobial drugs or supplements. Its bioactive compounds have demonstrated broad-spectrum activity against bacteria, fungi, and viruses, making them strong candidates for novel treatments. Given the escalating threat of AMR, <italic>Ganoderma</italic>&#x2019;s multi-target mechanisms&#x2014;including cell wall disruption, nucleic acid synthesis inhibition, and oxidative stress induction&#x2014;could provide alternative therapies that pathogens struggle to resist. Perhaps most compelling is the potential for <italic>Ganoderma</italic> to enhance conventional antibiotics through synergistic combinations. Preliminary evidence suggests that pairing <italic>Ganoderma</italic> extracts with existing antimicrobials may improve efficacy while reducing required dosages, thereby minimizing side effects and delaying resistance. Future research should systematically investigate these interactions, particularly against drug-resistant strains, as well as explore the role of <italic>Ganoderma</italic> as an adjunct therapy for fungal and viral infections in immunocompromised patients. By addressing these priorities, <italic>Ganoderma</italic> could transition from a traditional remedy to a scientifically validated antimicrobial agent, offering new solutions in an era of increasing treatment challenges.</p>
</sec>
<sec id="s10" sec-type="conclusions">
<label>10</label>
<title>Conclusion</title>
<p>
<italic>Ganoderma</italic> exhibits significant promise as a natural source of antimicrobial agents, with its bioactive compounds&#x2014;polysaccharides, triterpenoids, phenolic compounds, and proteins&#x2014;demonstrating a variety of mechanisms to combat bacterial, fungal, and viral infections. These compounds function by disrupting microbial cell walls, inhibiting nucleic acid synthesis, modulating the immune system, and regulating oxidative stress, offering a multi-targeted approach to pathogen inhibition. However, it is important to note that there may be potential risks or limitations associated with the use of <italic>Ganoderma</italic> as an antimicrobial agent, which should be thoroughly investigated in future research. Numerous <italic>in vitro</italic> and preclinical studies have already illustrated <italic>Ganoderma</italic>&#x2019;s potential to be developed into therapeutic agents, especially in light of the growing global concern over AMR. Future research should prioritize clinical trials to validate <italic>Ganoderma</italic>&#x2019;s efficacy in human subjects, particularly for its antimicrobial applications. Standardizing <italic>Ganoderma</italic> extracts is another critical area that would facilitate consistency in research and therapeutic use. In addition, identifying and isolating specific active compounds within <italic>Ganoderma</italic> may allow for more targeted drug development, potentially leading to the creation of new antimicrobial drugs or supplements. Furthermore, exploring synergistic effects with conventional antibiotics could offer new solutions to enhance treatment efficacy and reduce drug resistance. Continued investigation into these areas will be key to unlocking <italic>Ganoderma</italic>&#x2019;s full potential as a vital player in the future of antimicrobial therapies.</p>
</sec>
</body>
<back>
<sec id="s11" sec-type="author-contributions">
<title>Author contributions</title>
<p>SK: Conceptualization, Investigation, Methodology, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. NP: Methodology, Software, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. KH: Conceptualization, Investigation, Methodology, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing. IP: Conceptualization, Methodology, Writing &#x2013; original draft, Writing &#x2013; review &amp; editing.</p>
</sec>
<sec id="s12" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. Samantha C. Karunarathna thanks the High-Level Talent Recruitment Plan of Yunnan Province (&#x201c;High-End Foreign Experts&#x201d; Program), the National Natural Science Foundation of China (Grant No. 32260004), and Key Laboratory of Yunnan Provincial Department of Education of the Deep-Time Evolution on Biodiversity from the Origin of the Pearl River, Qujing Normal University, Qujing, Yunnan 655011, China, for their support. We also extend our gratitude to Chiang Mai University, Thailand, for partial support of this research.</p>
</sec>
<sec id="s13" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s14" sec-type="ai-statement">
<title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
</sec>
<sec id="s15" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors&#xa0;and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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