Alternative sulphur metabolism in the fungal pathogen Candida parapsilosis.

Autor: Lombardi L; School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland. lisa.lombardi@ucd.ie., Salzberg LI; School of Medicine, Conway Institute, University College Dublin, Belfield, Dublin, Ireland., Cinnéide EÓ; School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland., O'Brien C; School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland., Morio F; Nantes Université, CHU Nantes, Cibles et Médicaments des Infections et de l'Immunité, UR1155, Nantes, France., Turner SA; School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland., Byrne KP; School of Medicine, Conway Institute, University College Dublin, Belfield, Dublin, Ireland., Butler G; School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland. gbutler@ucd.ie.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 24; Vol. 15 (1), pp. 9190. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1038/s41467-024-53442-8
Abstrakt: Candida parapsilosis is an opportunistic fungal pathogen commonly isolated from the environment and associated with nosocomial infection outbreaks worldwide. We describe here the construction of a large collection of gene disruptions, greatly increasing the molecular tools available for probing gene function in C. parapsilosis. We use these to identify transcription factors associated with multiple metabolic pathways, and in particular to dissect the network regulating the assimilation of sulphur. We find that, unlike in other yeasts and filamentous fungi, the transcription factor Met4 is not the main regulator of methionine synthesis. In C. parapsilosis, assimilation of inorganic sulphur (sulphate) and synthesis of cysteine and methionine is regulated by Met28, a paralog of Met4, whereas Met4 regulates expression of a wide array of transporters and enzymes involved in the assimilation of organosulfur compounds. Analysis of transcription factor binding sites suggests that Met4 is recruited by the DNA-binding protein Met32, and Met28 is recruited by Cbf1. Despite having different target genes, Met4 and Met28 have partial functional overlap, possibly because Met4 can contribute to assimilation of inorganic sulphur in the absence of Met28.
(© 2024. The Author(s).)
Databáze: MEDLINE
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