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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
08:45

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

Published on: December 28, 2017

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Genetic Drivers of Multidrug Resistance in Candida glabrata

Kelley R Healey1, Cristina Jimenez Ortigosa1, Erika Shor1

  • 1Public Health Research Institute, Rutgers Biomedical and Health Sciences, New Jersey Medical School Newark, NJ, USA.

Frontiers in Microbiology
|December 27, 2016
PubMed

Insights

Candida glabrata rapidly develops antifungal resistance through genetic diversity and chromosomal changes. Mutations in MSH2 and chromosomal rearrangements contribute to increased drug resistance in this opportunistic fungal pathogen.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance
  • Genetics and Genomics

Background:

  • Rising incidence of invasive fungal infections.
  • Increasing multidrug resistance in Candida glabrata.
  • Need to understand resistance mechanisms in Candida glabrata.

Purpose of the Study:

  • Discuss mechanisms of rapid multidrug resistance development in Candida glabrata.
  • Highlight the role of genetic diversity and chromosomal instability.
  • Analyze the population structure and genomic variation in clinical isolates.

Main Methods:

  • Analysis of genetic diversity in clinical Candida glabrata isolates.
  • Investigation of mutations in the DNA mismatch repair gene MSH2.
  • Documentation of chromosomal rearrangements using serial isolates from patients undergoing antifungal treatment.

Main Results:

  • Over 50% of clinical strains exhibit MSH2 mutations, leading to a mutator phenotype and increased drug-resistant mutants in vitro.
  • Extensive chromosomal rearrangements result in diverse karyotypes within the species.
  • Chromosomal changes in Candida glabrata were observed in vivo during antifungal treatment.
  • MSH2 genotypes and chromosomal patterns correlate with specific strain types, indicating a complex population structure.

Conclusions:

  • Genetic diversity, particularly MSH2 mutations and chromosomal rearrangements, drives rapid antifungal resistance in Candida glabrata.
  • Candida glabrata possesses a complex population structure facilitating adaptation and persistence of genomic variants.
  • Understanding these mechanisms is crucial for combating invasive fungal infections caused by Candida glabrata.
Keywords:
Candida glabrataDNA repairMLST genotypingMSH2antifungal resistanceechinocandinskaryotypingtriazoles

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