PmZapA orchestrates zinc homeostasis and pleiotropic stress responses to drive pathogenicity in Talaromyces marneffei
- 1School of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan University, Haikou, Hainan, China
- 2Shenzhen Key Laboratory of Microbiology in Genomic Modification & Editing and Application, Shenzhen University Medical School, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China
- 3Faculty of Health Sciences, University of Macau, Macau SAR, China
Abstract
Zinc homeostasis is critical for pathogenic microbes during their interactions with hosts. In Aspergillus nidulans, the transcription factor ZapA serves as a key regulator of zinc uptake. However, the function of ZapA in the thermally dimorphic pathogen Talaromyces marneffei remains largely unexplored. In this study, we identified and characterized the ZapA homolog in T. marneffei. Our results demonstrate that PmZapA acts as a master regulator of zinc homeostasis by directly controlling the expression of the zinc transporter encoding genes. Deletion of PmzapA severely impaired growth under Zinc – conditions and reduced pigment production. Notably, in a Galleria mellonella larval infection model, the ΔPmzapA strain exhibited significantly attenuated virulence. However, the reduced pathogenicity was not solely attributable to defective zinc transport, as additional pleiotropic effects were detected. Specifically, the ΔPmzapA strain showed impaired reactive oxygen species (ROS) clearance capability, as well as increased susceptibility to cell wall stress and alkaline pH. Integrated RNA-seq and ChIP-seq analysis revealed that PmZapA governs a broad regulatory network, directly and indirectly modulating pathways involved in redox homeostasis, secondary metabolite biosynthesis, as well as carbon metabolism. Collectively, our work identifies PmZapA as a novel virulence determinant in T. marneffei.
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BibTeX
@article{shen2026pmzapa,
title = {{PmZapA orchestrates zinc homeostasis and pleiotropic stress responses to drive pathogenicity in Talaromyces marneffei}},
author = {Qi Shen and Yuan Nong and Zhengqiang Miao and Jianwei Ma and Lei Peng and Shi Chen and Fang Wang},
journal = {Virulence},
year = {2026},
month = oct,
doi = {10.1080/21505594.2026.2753296},
url = {https://doi.org/10.1080/21505594.2026.2753296},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - PmZapA orchestrates zinc homeostasis and pleiotropic stress responses to drive pathogenicity in Talaromyces marneffei
AU - Qi Shen
AU - Yuan Nong
AU - Zhengqiang Miao
AU - Jianwei Ma
AU - Lei Peng
AU - Shi Chen
AU - Fang Wang
PY - 2026
DA - 2026/10/27
JO - Virulence
DO - 10.1080/21505594.2026.2753296
UR - https://doi.org/10.1080/21505594.2026.2753296
AB - Zinc homeostasis is critical for pathogenic microbes during their interactions with hosts. In Aspergillus nidulans, the transcription factor ZapA serves as a key regulator of zinc uptake. However, the function of ZapA in the thermally dimorphic pathogen Talaromyces marneffei remains largely unexplored. In this study, we identified and characterized the ZapA homolog in T. marneffei. Our results demonstrate that PmZapA acts as a master regulator of zinc homeostasis by directly controlling the expression of the zinc transporter encoding genes. Deletion of PmzapA severely impaired growth under Zinc – conditions and reduced pigment production. Notably, in a Galleria mellonella larval infection model, the ΔPmzapA strain exhibited significantly attenuated virulence. However, the reduced pathogenicity was not solely attributable to defective zinc transport, as additional pleiotropic effects were detected. Specifically, the ΔPmzapA strain showed impaired reactive oxygen species (ROS) clearance capability, as well as increased susceptibility to cell wall stress and alkaline pH. Integrated RNA-seq and ChIP-seq analysis revealed that PmZapA governs a broad regulatory network, directly and indirectly modulating pathways involved in redox homeostasis, secondary metabolite biosynthesis, as well as carbon metabolism. Collectively, our work identifies PmZapA as a novel virulence determinant in T. marneffei.
SN - 2150-5594
SN - 2150-5608
ER -