The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation.

Autor: Xie JL; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1., Qin L; Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China., Miao Z; Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China., Grys BT; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, M5S 3E1., Diaz JC; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, 14642, USA., Ting K; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1., Krieger JR; The Hospital for Sick Children, SPARC Biocentre, Toronto, ON, Canada, M5G 0A4., Tong J; The Hospital for Sick Children, Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada, M5G 0A4., Tan K; Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China., Leach MD; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1.; Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Abderdeen, AB252ZD, UK., Ketela T; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1., Moran MF; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1.; The Hospital for Sick Children, SPARC Biocentre, Toronto, ON, Canada, M5G 0A4.; The Hospital for Sick Children, Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada, M5G 0A4., Krysan DJ; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, 14642, USA.; Department of Pediatrics and Microbiology/Immunology, University of Rochester, Rochester, NY, 14642, USA., Boone C; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, M5S 3E1., Andrews BJ; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1.; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, M5S 3E1., Selmecki A; Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, 68178, USA., Ho Wong K; Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China., Robbins N; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1., Cowen LE; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1. leah.cowen@utoronto.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2017 Sep 11; Vol. 8 (1), pp. 499. Date of Electronic Publication: 2017 Sep 11.
DOI: 10.1038/s41467-017-00547-y
Abstrakt: The capacity to coordinate environmental sensing with initiation of cellular responses underpins microbial survival and is crucial for virulence and stress responses in microbial pathogens. Here we define circuitry that enables the fungal pathogen Candida albicans to couple cell cycle dynamics with responses to cell wall stress induced by echinocandins, a front-line class of antifungal drugs. We discover that the C. albicans transcription factor Cas5 is crucial for proper cell cycle dynamics and responses to echinocandins, which inhibit β-1,3-glucan synthesis. Cas5 has distinct transcriptional targets under basal and stress conditions, is activated by the phosphatase Glc7, and can regulate the expression of target genes in concert with the transcriptional regulators Swi4 and Swi6. Thus, we illuminate a mechanism of transcriptional control that couples cell wall integrity with cell cycle regulation, and uncover circuitry governing antifungal drug resistance.Cas5 is a transcriptional regulator of responses to cell wall stress in the fungal pathogen Candida albicans. Here, Xie et al. show that Cas5 also modulates cell cycle dynamics and responses to antifungal drugs.
Databáze: MEDLINE