Homeostatic control of an iron repressor in a GI tract resident

  1. Yuanyuan Wang
  2. Yinhe Mao
  3. Xiaoqing Chen
  4. Xinhuang Huang
  5. Zhongyi Jiang
  6. Kaiyan Yang
  7. Lixing Tian
  8. Tong Jiang
  9. Yun Zou
  10. Xiaoyuan Ma
  11. Chaoyue Xu
  12. Zili Zhou
  13. Xianwei Wu
  14. Lei Pan
  15. Huaping Liang  Is a corresponding author
  16. Lin Zhong  Is a corresponding author
  17. Changbin Chen  Is a corresponding author
  1. Institut Pasteur of Shanghai, China
  2. Shanghai Jiao Tong University, China
  3. Army Medical University, China

Abstract

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 (GI) 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 (PTMs) 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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all Figures.

Article and author information

Author details

  1. Yuanyuan Wang

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Yinhe Mao

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiaoqing Chen

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Xinhuang Huang

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Zhongyi Jiang

    Department of General Surgery, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Kaiyan Yang

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Lixing Tian

    State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Tong Jiang

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yun Zou

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Xiaoyuan Ma

    State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Chaoyue Xu

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Zili Zhou

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Xianwei Wu

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Lei Pan

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Huaping Liang

    State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, China
    For correspondence
    13638356728@163.com
    Competing interests
    The authors declare that no competing interests exist.
  16. Lin Zhong

    Department of General Surgery, Shanghai Jiao Tong University, Shanghai, China
    For correspondence
    zhonglin1@medmail.com.cn
    Competing interests
    The authors declare that no competing interests exist.
  17. Changbin Chen

    The Center for Microbes, Development and Health, Institut Pasteur of Shanghai, Shanghai, China
    For correspondence
    cbchen@ips.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7961-3488

Funding

The MOST Key R&D Program of China (2022YFC2303200)

  • Changbin Chen

The National Natural Science Foundation (31600119)

  • Xinhuang Huang

The Natural Science Foundation of Shanghai (20ZR1463800)

  • Xinhuang Huang

The Natural Science Foundation of Shanghai (15ZR1444400)

  • Xinhuang Huang

The MOST Key R&D Program of China (2022YFC2304700)

  • Lin Zhong

The National Natural Science Foundation (32170195)

  • Changbin Chen

The Shanghai Municipal Science and Technology Major Project (2019SHZDZX02)

  • Changbin Chen

The Open Project of the State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (SKLKF201803)

  • Changbin Chen

The Special Program of PLA (19SWAQ18)

  • Huaping Liang

National Postdoctoral Fellowship (No.312780)

  • Yuanyuan Wang

Shanghai Post-doctoral Excellence Program (No.2022647)

  • Yuanyuan Wang

The National Natural Science Foundation (32070146)

  • Xinhuang Huang

The funders had role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were carried out in strict accordance with the regulations in the Guide for the Care and Use of Laboratory Animals issued by the Ministry of Science and Technology of the People's Republic of China. All efforts were made to minimize suffering. The protocol was approved by IACUC at the Institut Pasteur of Shanghai, Chinese Academy of Sciences (Permit Number: A160291).

Reviewing Editor

  1. Antonis Rokas, Vanderbilt University, United States

Publication history

  1. Received: January 10, 2023
  2. Accepted: May 24, 2023
  3. Accepted Manuscript published: May 25, 2023 (version 1)

Copyright

© 2023, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yuanyuan Wang
  2. Yinhe Mao
  3. Xiaoqing Chen
  4. Xinhuang Huang
  5. Zhongyi Jiang
  6. Kaiyan Yang
  7. Lixing Tian
  8. Tong Jiang
  9. Yun Zou
  10. Xiaoyuan Ma
  11. Chaoyue Xu
  12. Zili Zhou
  13. Xianwei Wu
  14. Lei Pan
  15. Huaping Liang
  16. Lin Zhong
  17. Changbin Chen
(2023)
Homeostatic control of an iron repressor in a GI tract resident
eLife 12:e86075.
https://doi.org/10.7554/eLife.86075

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