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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Healey, KR; Zhao, Y; Perez, WB; Lockhart, SR; Sobel, JD; Farmakiotis, D; Kontoyiannis, DP; Sanglard, D; Taj-Aldeen, SJ; Alexander, BD; Jimenez-Ortigosa, C; Shor, E; Perlin, DS

Published Date

  • March 29, 2016

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 11128 -

PubMed ID

  • 27020939

Pubmed Central ID

  • 27020939

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms11128

Language

  • eng

Conference Location

  • England