Global Stress Responses Identify the Functionally Divergent Regulators Required for <i>Candida auris</i> Commensalism and Pathogenicity
Given its global distribution and high transmissibility in the environment, <i>Candida auris</i> poses a serious threat to global public health. However, the underlying mechanisms of its adaptive strategies remain poorly understood. Here we delineate the pan-genome structures of 1,306 representative <i>C. auris</i> isolates collected from 28 countries. In addition to the clade-related genetic diversity and highly variable pan-genomes, we identify the key regulatory modules and genes specific to <i>C. auris</i> in response to 32 different host microenvironment-mimicking stresses. Through comparative analysis with evolutionarily close fungal relatives, we uncover both shared and species-specific transcriptional responses in <i>C. auris</i>. Intriguingly, our results reveal a distinct pathogenic role for the conserved iron regulon in this species. Unexpectedly, we also identify an evolutionarily divergent functional role for <i>RIM101</i> in regulating both pathogenicity and commensalism of <i>C. auris</i>. Mechanistically, the high-affinity glucose transporters were found to enhance the tolerance to alkaline stress through alleviation of <i>RIM101</i>-dependent glucose repression in the host microenvironment. These findings provide mechanistic insights into the evolutionarily divergent adaptive strategies in both commensalism and virulence of the emerging critical priority fungal pathogen, <i>C. auris</i>.
Authors
- Yueru Tian
- Xiaotian Huang (ORCID: https://orcid.org/0000-0003-1145-8386)
- Zhiyi He (ORCID: https://orcid.org/0000-0002-2953-0772)
- Chaoyue Xu
- Changbin Chen (ORCID: https://orcid.org/0000-0002-7961-3488)
- Yufeng Yuan (ORCID: https://orcid.org/0000-0003-3924-3803)
- Wanxing Xu (ORCID: https://orcid.org/0009-0008-8043-1658)
- Xiaoqi Zheng (ORCID: https://orcid.org/0000-0002-1832-4404)
- Ming Guan (ORCID: https://orcid.org/0000-0002-8861-1281)
- Yuping Zhang (ORCID: https://orcid.org/0000-0003-3336-7426)
- Ning‐Ning Liu (ORCID: https://orcid.org/0000-0002-1468-6897)
- Yun Zou
- Dongsheng Zhou (ORCID: https://orcid.org/0000-0003-3827-5969)
- Guangsheng Chen (ORCID: https://orcid.org/0000-0001-6544-5287)
- Zili Zhou (ORCID: https://orcid.org/0009-0004-2259-8290)
- Lingfei Hu (ORCID: https://orcid.org/0000-0001-7287-6800)
- Yuanyuan Wang (ORCID: https://orcid.org/0000-0001-7464-7446)
- Ouyang Mo (ORCID: https://orcid.org/0009-0000-2364-6021)
- Jihong Liu (ORCID: https://orcid.org/0000-0003-3464-2901)
- Luyao Zhang (ORCID: https://orcid.org/0000-0003-4009-4657)
- Lin Zhong
- Xiaoqing Chen (ORCID: https://orcid.org/0000-0002-2614-4948)
- Wenwen Xue
- Lingbing Zeng (ORCID: https://orcid.org/0000-0002-7073-0039)
- Yanmei Dong (ORCID: https://orcid.org/0000-0002-9154-8949)
- Zhe Yin
- Lei Wu (ORCID: https://orcid.org/0009-0006-0663-9560)
- Xinhua Huang
- Kunlin Li
- Pei Wen Hao
- Sichu Xiong
Institutions
- Nanchang University (CN)
- Guangxi Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Shanghai Normal University (CN)
- Fudan University (CN)
- Academy of Military Medical Sciences (CN)
- Nanjing Health and Health Commission (CN)
- Chinese People's Armed Police Force Medical College Affiliated Hospital (CN)
- First Affiliated Hospital of GuangXi Medical University (CN)
- Huashan Hospital (CN)
- First Affiliated Hospital of Nanchang University (CN)
- Institute of Infection and Immunity (CA)
- Shenzhen Third People’s Hospital (CN)
Publication Details
- Journal
- Exploration
- Published
- 2025-11-11
- DOI
- https://doi.org/10.1002/exp.20240482
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Shanghai Jiao Tong University
- State Key Laboratory of Pathogen and Biosecurity
- Program of Shanghai Academic Research Leader