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Nat Commun. 2016 Mar 29;7:11128. doi: 10.1038/ncomms11128.

Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance.

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Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey 07103, USA.
Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-11, Atlanta, Georgia 30333, USA.
Wayne State University School of Medicine, 540 E. Canfield Avenue, 1241 Scott Hall, Detroit, Michigan 48201, USA.
The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT12.5046, Unit 1463, Houston, Texas 77030, USA.
Warren Alpert Medical School of Brown University, 593 Eddy Street, Gerry House 113, Providence, Rhode Island 02903, USA.
Institute of Microbiology of the University Hospital of Lausanne, Rue Bugnon 48, CH-1011 Lausanne, Switzerland.
Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
Duke University, 315 Trent Drive, Hanes House, Room 163A, Durham, North Carolina 27710, USA.


The fungal pathogen Candida glabrata has emerged as a major health threat since it readily acquires resistance to multiple drug classes, including triazoles and/or echinocandins. Thus far, cellular mechanisms promoting the emergence of resistance to multiple drug classes have not been described in this organism. Here we demonstrate that a mutator phenotype caused by a mismatch repair defect is prevalent in C. glabrata clinical isolates. Strains carrying alterations in mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifungal treatment in vitro and in mouse models of colonization, and are recovered at a high rate (55% of all C. glabrata recovered) from patients. This genetic mechanism promotes the acquisition of resistance to multiple antifungals, at least partially explaining the elevated rates of triazole and multi-drug resistance associated with C. glabrata. We anticipate that identifying MSH2 defects in infecting strains may influence the management of patients on antifungal drug therapy.

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