<i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing Ferroptosis

Recent studies have shown that several pathogens manipulate ferroptosis in host cells to aid their dissemination and enhance pathogenicity. While bacterial virulence factors capable of inducing ferroptosis have been identified, no such factors have been reported for human fungal pathogens thus far....

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Main Authors: Gang Luo, Yongman Ma, Chunyi Chen, Yudie Hu, Chunchun Yan, Di Wang, Cong Wang, Yanyan Wang, Xichen Yu, Andriy Sibirny, Jun Yuan, Yingqian Kang
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Journal of Fungi
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Online Access:https://www.mdpi.com/2309-608X/11/5/342
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author Gang Luo
Yongman Ma
Chunyi Chen
Yudie Hu
Chunchun Yan
Di Wang
Cong Wang
Yanyan Wang
Xichen Yu
Andriy Sibirny
Jun Yuan
Yingqian Kang
author_facet Gang Luo
Yongman Ma
Chunyi Chen
Yudie Hu
Chunchun Yan
Di Wang
Cong Wang
Yanyan Wang
Xichen Yu
Andriy Sibirny
Jun Yuan
Yingqian Kang
author_sort Gang Luo
collection DOAJ
description Recent studies have shown that several pathogens manipulate ferroptosis in host cells to aid their dissemination and enhance pathogenicity. While bacterial virulence factors capable of inducing ferroptosis have been identified, no such factors have been reported for human fungal pathogens thus far. <i>Candida albicans</i>, a most common human pathogenic fungus causing invasive fungal diseases, has recently been found to be able to induce ferroptosis in macrophages. Whether specific virulence factors induce ferroptosis in host cells that promote <i>C. albicans</i> pathogenicity remains to be defined. Here, we identify <i>CVF1</i> as a critical virulence gene of <i>C. albicans</i> that is required for systemic fungal infection. Moreover, the <i>CVF1</i> gene can significantly promote macrophage death. Using a macrophage infection model combined with the addition of cell death inhibitors, we show that the <i>CVF1</i>-induced death of macrophages is attributed to ferroptosis. More importantly, <i>CVF1</i> is sufficient to trigger ferroptosis to promote <i>C. albicans</i> dissemination and pathogenicity in vivo. This study highlights a mechanism by which a virulence factor from a human fungal pathogen regulates ferroptosis in host cells, supporting the concept that human pathogenic fungi harbor specific virulence factors to manipulate ferroptosis in host cells for their invasive infection.
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spelling doaj-art-1b4a4733990d46259937e6a809ffcaac2025-08-20T03:47:54ZengMDPI AGJournal of Fungi2309-608X2025-04-0111534210.3390/jof11050342<i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing FerroptosisGang Luo0Yongman Ma1Chunyi Chen2Yudie Hu3Chunchun Yan4Di Wang5Cong Wang6Yanyan Wang7Xichen Yu8Andriy Sibirny9Jun Yuan10Yingqian Kang11Key Laboratory of Microbiology and Parasitology of Education Department of Guizhou, School of Basic Medical Science, Guizhou Medical University, Guiyang 561113, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Guizhou Medical University, Guiyang 561113, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 561113, ChinaKey Laboratory of Microbiology and Parasitology of Education Department of Guizhou, School of Basic Medical Science, Guizhou Medical University, Guiyang 561113, ChinaKey Laboratory of Microbiology and Parasitology of Education Department of Guizhou, School of Basic Medical Science, Guizhou Medical University, Guiyang 561113, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 561113, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 561113, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 561113, ChinaKey Laboratory of Microbiology and Parasitology of Education Department of Guizhou, School of Basic Medical Science, Guizhou Medical University, Guiyang 561113, ChinaInstitute of Cell Biology, NAS of Ukraine, Drahomanov Street 14/16, 79005 Lviv, UkraineDepartment of Laboratory Medicine, Guiyang Second People’s Hospital, Guiyang 550081, ChinaKey Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 561113, ChinaRecent studies have shown that several pathogens manipulate ferroptosis in host cells to aid their dissemination and enhance pathogenicity. While bacterial virulence factors capable of inducing ferroptosis have been identified, no such factors have been reported for human fungal pathogens thus far. <i>Candida albicans</i>, a most common human pathogenic fungus causing invasive fungal diseases, has recently been found to be able to induce ferroptosis in macrophages. Whether specific virulence factors induce ferroptosis in host cells that promote <i>C. albicans</i> pathogenicity remains to be defined. Here, we identify <i>CVF1</i> as a critical virulence gene of <i>C. albicans</i> that is required for systemic fungal infection. Moreover, the <i>CVF1</i> gene can significantly promote macrophage death. Using a macrophage infection model combined with the addition of cell death inhibitors, we show that the <i>CVF1</i>-induced death of macrophages is attributed to ferroptosis. More importantly, <i>CVF1</i> is sufficient to trigger ferroptosis to promote <i>C. albicans</i> dissemination and pathogenicity in vivo. This study highlights a mechanism by which a virulence factor from a human fungal pathogen regulates ferroptosis in host cells, supporting the concept that human pathogenic fungi harbor specific virulence factors to manipulate ferroptosis in host cells for their invasive infection.https://www.mdpi.com/2309-608X/11/5/342host–pathogen interactionsinvasive fungal infectionvirulence factorferroptosis
spellingShingle Gang Luo
Yongman Ma
Chunyi Chen
Yudie Hu
Chunchun Yan
Di Wang
Cong Wang
Yanyan Wang
Xichen Yu
Andriy Sibirny
Jun Yuan
Yingqian Kang
<i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing Ferroptosis
Journal of Fungi
host–pathogen interactions
invasive fungal infection
virulence factor
ferroptosis
title <i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing Ferroptosis
title_full <i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing Ferroptosis
title_fullStr <i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing Ferroptosis
title_full_unstemmed <i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing Ferroptosis
title_short <i>CVF1</i> Promotes Invasive <i>Candida albicans</i> Infection via Inducing Ferroptosis
title_sort i cvf1 i promotes invasive i candida albicans i infection via inducing ferroptosis
topic host–pathogen interactions
invasive fungal infection
virulence factor
ferroptosis
url https://www.mdpi.com/2309-608X/11/5/342
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