Back
Full-text
Journal article

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

  • Healey KR Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey 07103, USA.
  • Zhao Y Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey 07103, USA.
  • Perez WB Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey 07103, USA.
  • Lockhart SR Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-11, Atlanta, Georgia 30333, USA.
  • Sobel JD Wayne State University School of Medicine, 540 E. Canfield Avenue, 1241 Scott Hall, Detroit, Michigan 48201, USA.
  • Farmakiotis D The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT12.5046, Unit 1463, Houston, Texas 77030, USA.
  • Kontoyiannis DP The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT12.5046, Unit 1463, Houston, Texas 77030, USA.
  • Sanglard D Institute of Microbiology of the University Hospital of Lausanne, Rue Bugnon 48, CH-1011 Lausanne, Switzerland.
  • Taj-Aldeen SJ Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
  • Alexander BD Duke University, 315 Trent Drive, Hanes House, Room 163A, Durham, North Carolina 27710, USA.
  • Jimenez-Ortigosa C Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey 07103, USA.
  • Shor E Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey 07103, USA.
  • Perlin DS Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, 225 Warren Street, Rutgers, Newark, New Jersey 07103, USA.
Show more…
  • 2016-03-30
Published in:
  • Nature communications. - 2016
Animals
Antifungal Agents
Candida glabrata
Candidiasis
Colony Count, Microbial
Disease Models, Animal
Drug Resistance, Fungal
Drug Resistance, Multiple
Echinocandins
Gene Deletion
Genes, Fungal
Genotype
Humans
Kidney
Mice
Mutation
Phenotype
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/265335
Statistics
Document views: 21 File downloads:
  • Full-text: 0