Two clinical isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B both harbor mutations in ERG2

Antimicrob Agents Chemother. 2012 Dec;56(12):6417-21. doi: 10.1128/AAC.01145-12. Epub 2012 Oct 1.

Abstract

Two novel isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B (MIC, 8 μg ml(-1)) were found to be ERG2 mutants, wherein Δ(8)-sterol intermediates comprised >90% of the total cellular sterol fraction. Both harbored an alteration at Thr(121) in ERG2; the corresponding residue (Thr(119)) in Saccharomyces cerevisiae is essential for sterol Δ8-Δ7 isomerization. This constitutes the first report of C. glabrata harboring mutations in ERG2 and exhibiting reduced sensitivity to amphotericin B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amphotericin B / pharmacology*
  • Antifungal Agents / pharmacology*
  • Azoles / pharmacology
  • Candida glabrata / drug effects*
  • Candida glabrata / genetics*
  • Candidiasis / microbiology*
  • Drug Resistance, Fungal / genetics*
  • Fluconazole / pharmacology
  • Fungal Proteins / genetics*
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mutation
  • Pyrimidines / pharmacology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Steroid Isomerases / genetics*
  • Sterols / chemistry
  • Triazoles / pharmacology
  • Voriconazole

Substances

  • Antifungal Agents
  • Azoles
  • Fungal Proteins
  • Pyrimidines
  • Sterols
  • Triazoles
  • Amphotericin B
  • Fluconazole
  • Steroid Isomerases
  • Voriconazole