Datasets

Title	Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA
Organism
Number of Samples	12
Release Date	2022/03/25 00:00
Sequencing Types
Protocol Details

Title
Authors	Alings F, Scharmann K, Eggers C, Böttcher B, Sokołowski M, Shvetsova E, Sharma P, Roth J, Rashiti L, Glatt S, Brunke S, Leidel SA
Journal	Nucleic acids research
Publication Date	2023 Aug 25
Abstract	Fungal pathogens threaten ecosystems and human health. Understanding the molecular basis of their virulence is key to develop new treatment strategies. Here, we characterize NCS2, a point mutation identified in a clinical baker's yeast isolate. Ncs2 is essential for 2-thiolation of tRNA and the NCS2 mutation leads to increased thiolation at body temperature. NCS2* yeast exhibits enhanced fitness when grown at elevated temperatures or when exposed to oxidative stress, inhibition of nutrient signalling, and cell-wall stress. Importantly, Ncs2* alters the interaction and stability of the thiolase complex likely mediated by nucleotide binding. The absence of 2-thiolation abrogates the in vivo virulence of pathogenic baker's yeast in infected mice. Finally, hypomodification triggers changes in colony morphology and hyphae formation in the common commensal pathogen Candida albicans resulting in decreased virulence in a human cell culture model. These findings demonstrate that 2-thiolation of tRNA acts as a key mediator of fungal virulence and reveal new mechanistic insights into the function of the highly conserved tRNA-thiolase complex. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
PMC	PMC10450187
PMID	37462076
DOI

Alings et al. 2023 (PRJNA819978)