1. Microbiology and Infectious Disease

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
https://doi.org/10.7554/eLife.86075
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Cite this article
  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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  3. Download .RIS

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.

Reviewing Editor

  1. Antonis Rokas, Vanderbilt University, United States

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).

Version history

  1. Received: January 10, 2023
  2. Preprint posted: January 30, 2023 (view preprint)
  3. Accepted: May 24, 2023
  4. Accepted Manuscript published: May 25, 2023 (version 1)
  5. Version of Record published: June 8, 2023 (version 2)

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

Share this article

https://doi.org/10.7554/eLife.86075

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    Transcriptomic analyses demonstrated differing time courses of immune responses, with prolonged myeloid cell activity in HD at 1 wk after the first vaccination dose. HD also demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p<0.05). Anti-spike IgG remained elevated above baseline at 6 mo in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development.

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    Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance HD subjects comparable to healthy controls and identify transcriptomic and clinical predictors of anti-spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of ESRD.

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