ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1628448
This article is part of the Research TopicTargeting Major Human Fungal Pathogens: Novel Insights into Virulence and Antifungal TherapiesView all 5 articles
Puf4-mediated Oxidative Stress and Virulence Attenuation in Cryptococcus neoformans
Provisionally accepted
- 1Northern Theater General Hospital, shenyang, China
- 2Northeastern University, shenyang, China
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Cryptococcus neoformans is a ubiquitous environmental fungal pathogen whose pathogenicity is closely linked to its ability to adapt to host environments. The RNA-binding protein Puf4 plays a key role in regulating the cell wall of C. neoformans. However, the specific mechanisms by which Puf4 regulates metabolism and virulence remain unclear. In this study, we systematically investigated the role of Puf4 in the metabolism and virulence of C. neoformans using RNA sequencing (RNA-seq), biochemical analysis, and in vivo animal experiments. Colony-spotting assay assays show that Puf4 affects the cell membrane and oxidative stress. RNA-seq analysis revealed that Puf4 was enriched in key metabolic pathways, including carbohydrate metabolism, oxidative phosphorylation, and glycolysis. Biochemical analysis revealed that Puf4 overexpression led to significant increases in both total carbohydrate and glycogen content. Additionally, the Puf4-overexpressing strain showed elevated ROS levels, and reduced resistance to antimycin A, indicating decreased oxidative stress tolerance. Notably, Puf4 overexpression resulted in reduced capsule size and decreased L-DOPA production, accompanied by downregulated expression of the capsule-associated gene CAP10 and the melanin biosynthesis gene LAC1. In vivo animal experiments further confirmed that the virulence of the Puf4-overexpressing strain was significantly attenuated. These findings suggest that Puf4 may serve as a regulator linking metabolic status and pathogenic potential in C.neoformans, although the underlying mechanisms require further elucidation.
Keywords: Cryptococcus neoformans, RNA-Binding Protein, Carbohydrate Metabolism, Oxidative Stress, Fungal Virulence
Received: 14 May 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Suo, lei, Zhang and Zhang. 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) or licensor 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.
* Correspondence:
Wanli Zhang, Northeastern University, shenyang, China
He Zhang, Northern Theater General Hospital, shenyang, China
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