Coordinated regulation of pH alkalinization by two transcription factors promotes fungal commensalism and pathogenicity

As a clinically relevant opportunistic human fungal pathogen, Candida albicans is able to rapidly sense and adapt to changing microenvironments within the host, a process that is essential for its successful invasion and survival. Although studies have shown that the transcription factor Stp2 is the master regulator of environmental alkalinization, accumulating evidence supports a clear involvement of other participants in this adaptation process. Here, following a large-scale genetic screen, we identify the transcription factor Dal81 as an uncharacterized positive regulator of pH alkalinization in C. albicans. Dal81 influences the protein levels of Stp2. A mutant lacking DAL81 also fails to alkalinize both in vitro and in the phagolysosome, and this defective phenotype is further enhanced by deleting both factors in most cases. Notably, our results demonstrate that Dal81 physically interacts with Stp2 to co-regulate the expression of a broad set of downstream target genes related to metabolism of organic acids, oxoacids, carboxylic acids and amino acids. This coordinated regulation mode is required for the alkalinization process and plays a role in modulating commensalism and pathogenicity of C. albicans. Taken together, our findings elucidate the cooperative function of Dal81 with Stp2 in the nucleus to orchestrate the expression of downstream genes required for the survival and propagation of C. albicans in the host.

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Publication Details

Journal
Nature Communications
Published
2025-08-22
DOI
https://doi.org/10.1038/s41467-025-62953-x
Citations
1
Primary Topic
Antifungal resistance and susceptibility
Type
article
Field-Weighted Citation Impact
1.40

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article

Coordinated regulation of pH alkalinization by two transcription factors promotes fungal commensalism and pathogenicity

Xiaoqing Chen, Hao Li, Winnie Shum, Changbin Chen et al.
1 citations
Nature Communications
Antifungal resistance and susceptibility
1.40
article

Coordinated regulation of pH alkalinization by two transcription factors promotes fungal commensalism and pathogenicity

Xiaoqing Chen, Hao Li, Winnie Shum, Changbin Chen, Xianwei Wu, Tong Jiang, Zaijie Jiang, Yun Zou, Junbiao Dai, Yuanyuan Wang, Yuping Zhang, Shanshan Li, Luyao Zhang, Zhiyi He, Qing Guo, Wenwen Xue, Xinhua Huang, Lei Wu, Guang-Sheng Chen, Hexiang Huang, Kunlin Li, Munika Moses
article en
1 citations

Abstract

As a clinically relevant opportunistic human fungal pathogen, Candida albicans is able to rapidly sense and adapt to changing microenvironments within the host, a process that is essential for its successful invasion and survival. Although studies have shown that the transcription factor Stp2 is the master regulator of environmental alkalinization, accumulating evidence supports a clear involvement of other participants in this adaptation process. Here, following a large-scale genetic screen, we identify the transcription factor Dal81 as an uncharacterized positive regulator of pH alkalinization in C. albicans. Dal81 influences the protein levels of Stp2. A mutant lacking DAL81 also fails to alkalinize both in vitro and in the phagolysosome, and this defective phenotype is further enhanced by deleting both factors in most cases. Notably, our results demonstrate that Dal81 physically interacts with Stp2 to co-regulate the expression of a broad set of downstream target genes related to metabolism of organic acids, oxoacids, carboxylic acids and amino acids. This coordinated regulation mode is required for the alkalinization process and plays a role in modulating commensalism and pathogenicity of C. albicans. Taken together, our findings elucidate the cooperative function of Dal81 with Stp2 in the nucleus to orchestrate the expression of downstream genes required for the survival and propagation of C. albicans in the host.

Nature CommunicationsVol. 16(1)
Hebei Medical University (CN), Guangxi Medical University (CN), Xiamen University (CN), First Affiliated Hospital of Xiamen University (CN), Fourth Hospital of Hebei Medical University (CN), University of Saint Joseph (CN), Zhongshan Hospital of Xiamen University (CN), First Affiliated Hospital of GuangXi Medical University (CN), Institute of Infection and Immunity (CA), University of Chinese Academy of Sciences (CN)
Natural Science Foundation of Shanghai, National Natural Science Foundation of China, State Key Laboratory of Pathogen and Biosecurity, University of California, San Francisco
Openalex Percentile: Top 17%
Antifungal resistance and susceptibility
1.40
DOIOpen Access PDFOpenAlex
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