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<journal-id journal-id-type="publisher-id">Front. Microbiol.</journal-id>
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<journal-title>Frontiers in Microbiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Microbiol.</abbrev-journal-title>
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<issn pub-type="epub">1664-302X</issn>
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<publisher-name>Frontiers Media S.A.</publisher-name>
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<article-id pub-id-type="doi">10.3389/fmicb.2026.1807695</article-id>
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<subj-group subj-group-type="heading">
<subject>Editorial</subject>
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<title-group>
<article-title>Editorial: Advancing antimicrobial strategies: nucleic acid and peptide-based approaches</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Azevedo</surname> <given-names>Nuno F.</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
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<uri xlink:href="https://loop.frontiersin.org/people/47978"/>
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<contrib contrib-type="author">
<name><surname>Obuobi</surname> <given-names>Sybil</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role>
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<contrib contrib-type="author">
<name><surname>Tram</surname> <given-names>Nhan Dai Thien</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name><surname>Nielsen</surname> <given-names>Peter E.</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
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<aff id="aff1"><label>1</label><institution>LEPABE, ALiCE, Faculty of Engineering, University of Porto</institution>, <city>Porto</city>, <country country="pt">Portugal</country></aff>
<aff id="aff2"><label>2</label><institution>Drug Transport and Delivery Research Group, The Department of Pharmacy, UiT The Arctic University of Norway</institution>, <city>Troms&#x000F8;</city>, <country country="no">Norway</country></aff>
<aff id="aff3"><label>3</label><institution>Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore</institution>, <city>Singapore</city>, <country country="sg">Singapore</country></aff>
<aff id="aff4"><label>4</label><institution>Department of Cellular and Molecular Medicine, Kobenhavns Universitet</institution>, <city>Copenhagen</city>, <country country="dk">Denmark</country></aff>
<author-notes>
<corresp id="c001"><label>&#x0002A;</label>Correspondence: Nuno F. Azevedo, <email xlink:href="mailto:nazevedo@fe.up.pt">nazevedo@fe.up.pt</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-03-03">
<day>03</day>
<month>03</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year>
</pub-date>
<volume>17</volume>
<elocation-id>1807695</elocation-id>
<history>
<date date-type="received">
<day>09</day>
<month>02</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>02</month>
<year>2026</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2026 Azevedo, Obuobi, Tram and Nielsen.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Azevedo, Obuobi, Tram and Nielsen</copyright-holder>
<license>
<ali:license_ref start_date="2026-03-03">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. 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.</license-p>
</license>
</permissions>
<kwd-group>
<kwd>antimicrobial resistance (AMR)</kwd>
<kwd>cell penetrating peptide (CPP)</kwd>
<kwd>nucleic acids</kwd>
<kwd>antimicrobial peptides</kwd>
<kwd>microbial infections</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. Sybil Obuobi acknowledges funding from the Troms&#x000F8; Research Foundation (TFS) through its TFS starting grant (20_SG_SO).</funding-statement>
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<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Antimicrobials, Resistance and Chemotherapy</meta-value>
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<notes notes-type="frontiers-research-topic">
<p>Editorial on the Research Topic <ext-link xlink:href="https://www.frontiersin.org/research-topics/64309/advancing-antimicrobial-strategies-nucleic-acid-and-peptide-based-approaches" ext-link-type="uri">Advancing antimicrobial strategies: nucleic acid and peptide-based approaches</ext-link></p></notes>
</front>
<body>
<p>The rise of antimicrobial resistance is a global threat, steadily eroding the effectiveness of existing antibiotics and limiting treatment options. This Research Topic brings together recent advancements in nucleic acid- and peptide-based approaches exploited for the control of infectious pathogens. More specifically, aspects such as mechanisms of action and assessment of effects on bacterial proliferation and virulence for a range of pathogens are described here.</p>
<p>The majority of the original research articles in this Research Topic are related to peptide-based approaches, which is likely a reflection of the larger number of research groups working with these molecules. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1569719">Giugliano et al.</ext-link> reported the use of pantinins (isolated from the venom of the <italic>Pandinus imperator</italic> scorpion) as a promising class of peptides that exert a membranolytic antimicrobial action against various clinical isolates of <italic>Klebsiella pneumoniae</italic>. This same microorganism was used as a target for 8 different peptides of human, insect, or synthetic origin (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1548362">Hanstein et al.</ext-link>). In another study, the D-Bac8c<sup>2, 5Leu</sup> peptide was shown to significantly reduce the viability of monospecies and polymicrobial biofilms of <italic>Staphylococcus aureus</italic> and <italic>Pseudomonas aeruginosa</italic> (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1571649">Shahrour et al.</ext-link>). Furthermore, D-Bac8c<sup>2, 5Leu</sup>-loaded hydrogel formulations provided sustained drug release and an enhanced antimicrobial activity. Another peptide, bacillomycin D, isolated from <italic>Bacillus amyloliquefaciens</italic>, also showed potent activity against the fungal pathogen <italic>Fusarium graminearum</italic> (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1599452">Liu et al.</ext-link>). In a related work, another antimicrobial lipopeptide and phytohormone complex powder prepared from <italic>B. amyloliquefaciens</italic> was also assessed for antimicrobial activity, aiming to treat Citrus Huanglongbing (HLB) disease (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2024.1458051">Ding et al.</ext-link>). Two strategies were assessed against extensively drug-resistant (XDR) Gram-negative pathogens. The first one involved a novel class of anthrocolins, with potent antimicrobial activities reported to interfere with amino acid metabolism in <italic>Pseudomonas aeruginosa</italic> (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1618419">Yang et al.</ext-link>), and another comprising the synergistic action between peptide-neomycin conjugates and polymyxin B (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1605813">Story et al.</ext-link>).</p>
<p>In addition, two contributions to this Research Topic describe advances in nucleic acid-based approaches. In one of them, engineered hammerhead ribozymes were directed against the mRNA of an essential gene of <italic>Escherichia coli</italic> (<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1663476">Miszkiewicz-Golec et al.</ext-link>). This promising approach allowed inhibition of bacterial growth by up to 70% over 24 h and enhanced tetracycline efficacy 2- to 4-fold. To assess their action, the ribozymes were incorporated into bacterial plasmids for future applications; however, a direct delivery method for the ribozymes to the bacteria still needs to be devised. In another study, <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1660799">Mendez et al.</ext-link> evaluated whether antisense phosphorodiamidate morpholino oligomers retain activity against biofilms of the <italic>Burkholderia cepacia</italic> complex (Bcc). These same oligomers had been previously conjugated with a peptide for delivery into bacterial cells and were active against planktonic bacteria. Using the same strategy, the authors concluded that the oligomer delivery and antimicrobial activity are still present to some extent within biofilms. In the future, <italic>in vivo</italic> studies should be performed to understand if these oligomers could become viable alternatives for the treatment of conditions such as pulmonary Bcc infections.</p>
<p>Finally, this Research Topic also includes two reviews. One, from <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1603380">Wojciechowska</ext-link>, described the application of endolysins, bacteriophage-encoded peptidoglycan hydrolases, and membrane-active peptides as next-generation antibacterial agents against Gram-negative bacteria; while another by <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fmicb.2025.1582863">Su et al.</ext-link> provided a general overview of antimicrobial peptides, including their original sources (e.g., animal- or plant-derived), along with their structure, optimization strategies, and main applications.</p>
<p>Collectively, these studies highlight the potential of nucleic acid- and peptide-based strategies to address resistant strains or polymicrobial infections via unique mechanisms, and will certainly assist in tackling the rise of antimicrobial resistance. We would like to thank the authors and co-authors of these articles for their valuable contributions to this field, and hope that the readers will enjoy this Research Topic.</p>
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<sec sec-type="author-contributions" id="s1">
<title>Author contributions</title>
<p>NA: Writing &#x02013; original draft. SO: Writing &#x02013; original draft. NT: Writing &#x02013; review &#x00026; editing. PN: Writing &#x02013; review &#x00026; editing.</p>
</sec>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
<p>The author(s) NA and SO declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.</p>
</sec>
<sec sec-type="ai-statement" id="s3">
<title>Generative AI statement</title>
<p>The author(s) declared that generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p></sec>
<sec sec-type="disclaimer" id="s4">
<title>Publisher&#x00027;s note</title>
<p>All claims expressed in this article are solely those of the authors 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>
<fn-group>
<fn fn-type="custom" custom-type="edited-by" id="fn0001">
<p>Edited and reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/19714/overview">Rustam Aminov</ext-link>, University of Aberdeen, United Kingdom</p>
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