Homeostatic control of an iron repressor in a GI tract resident

Yuanyuan Wang; Yinhe Mao; Xiaoqing Chen; Xinhuang Huang; Zhongyi Jiang; Kaiyan Yang; Lixing Tian; Tong Jiang; Yun Zou; Xiaoyuan Ma; Chaoyue Xu; Zili Zhou; Xianwei Wu; Lei Pan; Huaping Liang; Lin Zhong; Changbin Chen

doi:10.7554/eLife.86075

eLife (May 2023)

Homeostatic control of an iron repressor in a GI tract resident

Yuanyuan Wang,
Yinhe Mao,
Xiaoqing Chen,
Xinhuang Huang,
Zhongyi Jiang,
Kaiyan Yang,
Lixing Tian,
Tong Jiang,
Yun Zou,
Xiaoyuan Ma,
Chaoyue Xu,
Zili Zhou,
Xianwei Wu,
Lei Pan,
Huaping Liang,
Lin Zhong,
Changbin Chen

Affiliations

Yuanyuan Wang: ORCiD; The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Yinhe Mao: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China; The University of Chinese Academy of Sciences, Beijing, China
Xiaoqing Chen: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China; The University of Chinese Academy of Sciences, Beijing, China
Xinhuang Huang: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Zhongyi Jiang: Department of General Surgery, Shanghai General Hospital, Shanghai, China
Kaiyan Yang: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China; The University of Chinese Academy of Sciences, Beijing, China
Lixing Tian: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Army Medical Center (Daping Hospital), Chongqing, China
Tong Jiang: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Yun Zou: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Xiaoyuan Ma: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Army Medical Center (Daping Hospital), Chongqing, China
Chaoyue Xu: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China; College of Life Science, Shanghai, China
Zili Zhou: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Xianwei Wu: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China; The University of Chinese Academy of Sciences, Beijing, China
Lei Pan: The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Huaping Liang: State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Army Medical Center (Daping Hospital), Chongqing, China
Lin Zhong: Department of General Surgery, Shanghai General Hospital, Shanghai, China
Changbin Chen: ORCiD; The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Unit of Pathogenic Fungal Infection & Host Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China

DOI: https://doi.org/10.7554/eLife.86075
Journal volume & issue: Vol. 12

Abstract

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The transition metal iron plays a crucial role in living cells. However, high levels of iron are potentially toxic through the production of reactive oxygen species (ROS), serving as a deterrent to the commensal fungus Candida albicans for colonization in the iron-rich gastrointestinal tract. We observe that the mutant lacking an iron-responsive transcription factor Hap43 is hyper-fit for colonization in murine gut. We demonstrate that high iron specifically triggers multiple post-translational modifications and proteasomal degradation of Hap43, a vital process guaranteeing the precision of intestinal ROS detoxification. Reduced levels of Hap43 de-repress the expression of antioxidant genes and therefore alleviate the deleterious ROS derived from iron metabolism. Our data reveal that Hap43 functions as a negative regulator for oxidative stress adaptation of C. albicans to gut colonization and thereby provide a new insight into understanding the interplay between iron homeostasis and fungal commensalism.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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