lunes, 18 de abril de 2016

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

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



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

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

Abstract

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.

PMID:
 
27020939
 
[PubMed - in process]

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