A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris.
Autor: | Yuchen Deng, Ming Xu, Shuaihu Li, Jian Bing, Qiushi Zheng, Guanghua Huang, Wanqing Liao, Weihua Pan, Li Tao |
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Jazyk: | angličtina |
Rok vydání: | 2024 |
Předmět: | |
Zdroj: | PLoS Pathogens, Vol 20, Iss 7, p e1012362 (2024) |
Druh dokumentu: | article |
ISSN: | 1553-7366 1553-7374 |
DOI: | 10.1371/journal.ppat.1012362 |
Popis: | Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid β-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection. |
Databáze: | Directory of Open Access Journals |
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