Journal Article

A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris

Tao, Li, Deng, Yuchen, Zheng, Qiushi, Liao, Wanqing, Huang, Guanghua, Xu, Ming, Li, Shuaihu, Pan, Weihua, Bing, Jian

2024

Overview

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 C 2 H 2 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 gfc1 Δ 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptation / Adaptation (Physiology) / Adaptation, Physiological / Animals / Biofilms / Biology and Life Sciences / Candida auris / Candida auris - genetics / Candida auris - metabolism / Candidiasis / Candidiasis - microbiology / Carbon / Carbon sources / Causes of / Cell culture / DNA damage / Evolution & development / Fatty acids / Filamentation / Fungal Proteins - genetics / Fungal Proteins - metabolism / Fungi / Gene deletion / Gene Expression Regulation, Fungal / Gene mutations / Gene sequencing / Genetic aspects / Genomic analysis / Genotype & phenotype / Glycerol / Glycerol - metabolism / Humans / Infections / Medicine and Health Sciences / Metabolism / Mice / Microbial metabolism / Microbiological research / Morphology / Multidrug resistance / Mutation / Oxidation / Pathogens / Phenotypes / Physical Sciences / Point mutation / R&D / Research & development / Skin / Transcription Factors - genetics / Transcription Factors - metabolism / Whole genome sequencing / Yeast / Zinc finger proteins