Molecular Confirmation of the Relationship between Candida guilliermondii Fks1p Naturally Occurring Amino Acid Substitutions and Its Intrinsic Reduced Echinocandin Susceptibility

Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02644-16. doi: 10.1128/AAC.02644-16. Print 2017 May.

Abstract

Candida guilliermondii shows intrinsic reduced echinocandin susceptibility. It harbors two polymorphisms (L633M and T634A) in the Fks1p hot spot 1 region. Our objective was to confirm that the reduced echinocandin susceptibility of C. guilliermondii is due to those naturally occurring substitutions. We constructed a Saccharomyces cerevisiae mutant in which a region of the FKS1 gene (including hot spot 1) was replaced with that from C. guilliermondii The chimeric mutants showed 32-fold increases in echinocandin MIC values, confirming the hypothesis.

Keywords: Candida guilliermondii; FKS mutations; echinocandin resistance; molecular mechanism.

MeSH terms

  • Amino Acid Substitution / genetics
  • Antifungal Agents / pharmacology*
  • Base Sequence
  • Candida / drug effects*
  • Candida / genetics*
  • Candidiasis / drug therapy*
  • Drug Resistance, Fungal / genetics
  • Echinocandins / genetics
  • Echinocandins / pharmacology*
  • Glucosyltransferases / genetics*
  • Membrane Proteins / genetics*
  • Microbial Sensitivity Tests
  • Polymorphism, Single Nucleotide / genetics
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*

Substances

  • Antifungal Agents
  • Echinocandins
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Glucosyltransferases
  • FKS1 protein, S cerevisiae