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


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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Publication Info

Healey, Kelley R, Yanan Zhao, Winder B Perez, Shawn R Lockhart, Jack D Sobel, Dimitrios Farmakiotis, Dimitrios P Kontoyiannis, Dominique Sanglard, et al. (2016). Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance. Nature communications, 7(1). p. 11128. 10.1038/ncomms11128 Retrieved from

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Barbara Dudley Alexander

Professor of Medicine

Clinical research related to infectious complications of solid organ and bone marrow transplantation, with a particular interest in the treatment and rapid diagnosis of fungal disease. Training the next generation of Transplant Infectious Disease Physicians is a special focus of mine as the Principal Investigator of our Interdisciplinary T32 Training Program funded the NIH. 

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