Homeostatic control of an iron repressor in a GI tract resident
- Institut Pasteur of Shanghai, China
- Shanghai Jiao Tong University, China
- 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.
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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.
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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).
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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