Nucleic Acids Research · 12 authors, 20 centres
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This preclinical study used mouse infection and human cell culture models to show that a point mutation (Ncs2*) in pathogenic yeast increases tRNA thiolation and enhances fitness under stress, while the absence of this modification reduces fungal virulence.
The study characterized a point mutation (NCS2*) in pathogenic yeast that enhances 2-thiolation of tRNA at body temperature. This mutation increased yeast fitness under various stress conditions, including high temperature and oxidative stress, and altered the stability of the tRNA thiolase complex. In a mouse infection model, the absence of tRNA 2-thiolation (via deletion of NCS2 or NCS6) completely abrogated the in vivo virulence of pathogenic baker's yeast. Furthermore, in Candida albicans, the lack of this modification triggered changes in colony morphology and hyphae formation, leading to decreased virulence in a human epithelial cell culture model. The findings demonstrate that tRNA 2-thiolation is a key mediator of fungal virulence, suggesting that targeting tRNA modification enzymes could be a novel antifungal strategy.
