Alternative sulphur metabolism in the fungal pathogen Candida parapsilosis

• Published in: Nature communications 2024-10, Vol.15 (1), p.9190-17, Article 9190
• Main Authors: Lombardi, Lisa, Salzberg, Letal I., Cinnéide, Eoin Ó, O’Brien, Caoimhe, Morio, Florent, Turner, Siobhán A., Byrne, Kevin P., Butler, Geraldine
• Format: Article
• Language: English
• Subjects: 38; 38/90; 38/91; 45; 45/41; 45/70; 49; 631/208/191; 631/208/200; 631/326/193/2538; 631/326/193/2543; 631/326/421; Assimilation; Binding sites; Candida parapsilosis; Candida parapsilosis - genetics; Candida parapsilosis - metabolism; Cysteine - metabolism; DNA-binding protein; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; Gene expression; Gene Expression Regulation, Fungal; Gene regulation; Hospitals; Humanities and Social Sciences; Metabolic Networks and Pathways - genetics; Metabolic pathways; Metabolism; Methionine; Methionine - metabolism; multidisciplinary; Nosocomial infection; Nosocomial infections; Opportunist infection; Organosulfur compounds; Outbreaks; Pathogens; Protein arrays; Protein transport; Science; Science (multidisciplinary); Sulfates - metabolism; Sulfur; Sulfur - metabolism; Synthesis; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-53442-8

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. The fungus Candida parapsilosis is found in the environment and associated with nosocomial infection outbreaks. Here, Lombardi et al. generate a large collection of gene disruptions in this opportunistic pathogen and identify transcription factors associated with multiple metabolic pathways, revealing unique features in the regulation of sulphur assimilation.