Alings, Fiona; Scharmann, Karin; Eggers, Cristian; Böttcher, Bettina; Sokołowski, Mikołaj; Shvetsova, Ekaterina; Sharma, Puneet; Roth, Joël; Rashiti, Leon; Glatt, Sebastian; Brunke, Sascha; Leidel, Sebastian A (2023). Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA. Nucleic acids research, 51(15), pp. 8133-8149. Oxford University Press 10.1093/nar/gkad564
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Eggers Aracena, Cristian Eduardo, Shvetsova, Ekaterina, Sharma, Puneet, Rashiti, Leon, Leidel, Sebastian Andreas |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
1362-4962 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
19 Jul 2023 09:27 |
Last Modified: |
26 Aug 2023 00:15 |
Publisher DOI: |
10.1093/nar/gkad564 |
PubMed ID: |
37462076 |
BORIS DOI: |
10.48350/184931 |
URI: |
https://boris.unibe.ch/id/eprint/184931 |
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