AUTHOR=Zheng Dongnan , Zhou Yifan , Xu Bin , Bu Wenxia , Wang Fengxu , Zhao Xinyuan , Xue Peng , Ma Yuanyuan 

TITLE=Polystyrene nanoparticles reduce the Cryptococcus neoformans virulence via induction of mitochondrial dysfunction

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1708192

DOI=10.3389/fcimb.2025.1708192

ISSN=2235-2988

ABSTRACT=IntroductionCryptococcus neoformans is a fungus that poses a significant threat to human health, with its polysaccharide capsule being a key virulence factor that can upregulate the expression of host gene ARG1, encoding arginase-1, which suppresses T-cell-mediated antifungal immune responses. Nanoplastics may cause oxidative and mitochondrial stress in mammalian cells, potentially impacting fungal physiology and pathogenic mechanisms as well.MethodsWe utilized mouse models and fungal burden assays to investigate the effects of polystyrene nanoparticles (PS-NPs) on C. neoformans infection. Mice were subjected to oropharyngeal aspiration of 50 μl of 80 nm PS-NPs at a concentration of 5 μg/μl, administered three times a week over a specified duration. To assess the impact of PS-NPs on C. neoformans mitochondria, we measured intracellular reactive oxygen species (ROS) levels, mitochondrial superoxide, mitochondrial membrane potential, and intracellular ATP levels in whole fungal cells. Additionally, we performed RNA-Seq analysis and metabolomics studies to evaluate the effects of PS-NPs at a concentration of 0.3 μg/μL on the RNA and metabolic profiles of C. neoformans mitochondria.ResultsOur study demonstrated that PS-NPs significantly prolonged the survival of mice infected with C. neoformans (P = 0.0058). PS-NPs exposure resulted in a 30% reduction in ARG1 mRNA expression and enhanced T-cell-mediated antifungal immunity. Additionally, PS-NPs inhibited fungal capsule formation by approximately 40% in infected mice and 70% in capsule induction medium. Given the close link between the mitochondria of C. neoformans and capsule formation, we further investigated the effects of PS-NPs on mitochondrial function. Exposure to PS-NPs led to mitochondrial dysfunction in C. neoformans, as evidenced by a threefold increase in ROS, a 1.7-fold increase in mitochondrial membrane potential, and disruptions in mitochondrial transcription and metabolism.ConclusionThese results suggest that PS-NPs inhibit the formation of the C. neoformans capsule, potentially by inducing mitochondrial dysfunction. Furthermore, the findings highlight the broader implications of PS-NPs on fungal virulence and the dynamics of host-pathogen interactions, underscoring their significance in advancing our understanding of these complex relationships.