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

Jinglin L Xie; Longguang Qin; Zhengqiang Miao; Ben T Grys; Jacinto De La Cruz Diaz; Kenneth Ting; Jonathan R Krieger; Jiefei Tong; Kaeling Tan; Michelle D Leach; Troy Ketela; Michael F Moran; Damian J Krysan; Charles Boone; Brenda J Andrews; Anna Selmecki; Koon Ho Wong; Nicole Robbins; Leah E Cowen

doi:10.1038/s41467-017-00547-y

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

Journal article

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

Jinglin L Xie, Longguang Qin, Zhengqiang Miao, Ben T Grys, Jacinto De La Cruz Diaz, Kenneth Ting, Jonathan R Krieger, Jiefei Tong, Kaeling Tan, Michelle D Leach, …

Nature communications, Vol.8(1), 499

09/11/2017

DOI: 10.1038/s41467-017-00547-y

PMCID: PMC5593949

PMID: 28894103

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Abstract

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.

Mutation

Phosphorylation

Antifungal Agents - pharmacology

Cell Wall - genetics

Candida albicans - metabolism

Drug Resistance, Fungal - genetics

Transcription Factors - genetics

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Candida albicans - genetics

Microbial Sensitivity Tests

Transcription Factors - metabolism

Gene Expression Regulation, Fungal - drug effects

beta-Glucans - metabolism

Candida albicans - drug effects

Cell Wall - metabolism

Cell Cycle Checkpoints - genetics

Gene Expression Regulation, Fungal - genetics

Echinocandins - pharmacology

Details

Title: Subtitle: The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation
Creators: Jinglin L Xie - Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1
Longguang Qin - Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China
Zhengqiang Miao - Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China
Ben T Grys - Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, M5S 3E1
Jacinto De La Cruz Diaz - Department of Microbiology and Immunology, University of Rochester, Rochester, NY, 14642, USA
Kenneth Ting - Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1
Jonathan R Krieger - The Hospital for Sick Children, SPARC Biocentre, Toronto, ON, Canada, M5G 0A4
Jiefei Tong - The Hospital for Sick Children, Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada, M5G 0A4
Kaeling Tan - Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China
Michelle D Leach - Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Abderdeen, AB252ZD, UK
Troy Ketela - Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1
Michael F Moran - The Hospital for Sick Children, Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada, M5G 0A4
Damian J Krysan - Department of Pediatrics and Microbiology/Immunology, University of Rochester, Rochester, NY, 14642, USA
Charles Boone - Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, M5S 3E1
Brenda J Andrews - Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada, M5S 3E1
Anna Selmecki - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, 68178, USA
Koon Ho Wong - Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China
Nicole Robbins - Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1
Leah E Cowen - Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5G 1M1. leah.cowen@utoronto.ca
Resource Type: Journal article
Publication Details: Nature communications, Vol.8(1), 499
DOI: 10.1038/s41467-017-00547-y
PMID: 28894103
PMCID: PMC5593949
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: R01 AI098450 / NIAID NIH HHS Wellcome Trust R25 GM064133 / NIGMS NIH HHS
Language: English
Date published: 09/11/2017
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093349202771

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