Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA.

Autor:	Alings F; Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Muenster, Germany., Scharmann K; Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Muenster, Germany., Eggers C; Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Muenster, Germany.; Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland., Böttcher B; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Jena, Germany.; Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Jena, Germany., Sokołowski M; Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland., Shvetsova E; Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland., Sharma P; Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Muenster, Germany.; Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland., Roth J; Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland., Rashiti L; Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland., Glatt S; Max Planck Research Group at the Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland., Brunke S; Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Jena, Germany., Leidel SA; Max Planck Research Group for RNA Biology, Max Planck Institute for Molecular Biomedicine, Muenster, Germany.; Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2023 Aug 25; Vol. 51 (15), pp. 8133-8149.
DOI:	10.1093/nar/gkad564
Abstrakt:	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.)
Databáze:	MEDLINE
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