Abstract

The Pleiotropic Drug Resistance (PDR) network is central to the drug response in fungi, and its overactivation is associated with drug resistance. However, gene regulation of the PDR network is not well understood. Here, we show that the histone chaperone Rtt106 and the chromatin remodeller SWI/SNF control expression of the PDR network genes and confer drug resistance. In Saccharomyces cerevisiae, Rtt106 specifically localises to PDR network gene promoters dependent on transcription factor Pdr3, but not Pdr1, and is essential for Pdr3-mediated basal expression of the PDR network genes, while SWI/SNF is essential for both basal and drug-induced expression. Also in the pathogenic fungus Candida glabrata, Rtt106 and SWI/SNF regulate drug-induced PDR gene expression. Consistently, loss of Rtt106 or SWI/SNF sensitises drug-resistant S. cerevisiae mutants and C. glabrata to antifungal drugs. Since they cooperatively drive PDR network gene expression, Rtt106 and SWI/SNF represent potential therapeutic targets to combat antifungal resistance.

The Pleiotropic Drug Resistance (PDR) network is central to drug response in fungi, and its overactivation is associated with drug resistance. Here the authors show that the chromatin remodeller SWI/SNF and the histone chaperone Rtt106 are important for PDR gene expression in fungi and therefore mediate resistance to antifungal drugs.

Details

Title
SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes
Author
Nikolov, Vladislav N 1 ; Dhara, Malavia 2 ; Kubota, Takashi 1   VIAFID ORCID Logo 

1  University of Aberdeen, Foresterhill, Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, Aberdeen, UK (GRID:grid.7107.1) (ISNI:0000 0004 1936 7291) 
2  University of Aberdeen, Foresterhill, Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, Aberdeen, UK (GRID:grid.7107.1) (ISNI:0000 0004 1936 7291); University of Exeter, MRC Centre for Medical Mycology, Geoffrey Pope Building, Exeter, UK (GRID:grid.8391.3) (ISNI:0000 0004 1936 8024) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-29591-z
ProQuest document ID
2649422595
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.