Article: article from journal or magazin.
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.
Animals, Antifungal Agents/pharmacology, Antifungal Agents/therapeutic use, Candida glabrata/genetics, Candida glabrata/isolation & purification, Candidiasis/drug therapy, Candidiasis/microbiology, Colony Count, Microbial, Disease Models, Animal, Drug Resistance, Fungal/drug effects, Drug Resistance, Fungal/genetics, Drug Resistance, Multiple/drug effects, Drug Resistance, Multiple/genetics, Echinocandins/pharmacology, Echinocandins/therapeutic use, Gene Deletion, Genes, Fungal, Genotype, Humans, Kidney/drug effects, Kidney/microbiology, Mice, Mutation/genetics, Phenotype
Web of science
Last modification date