Chromosome 5 of Human Pathogen Candida albicans Carries Multiple Genes for Negative Control of Caspofungin and Anidulafungin Susceptibility

Antimicrob Agents Chemother. 2016 Nov 21;60(12):7457-7467. doi: 10.1128/AAC.01888-16. Print 2016 Dec.

Abstract

Candida albicans is an important fungal pathogen with a diploid genome that can adapt to caspofungin, a major drug from the echinocandin class, by a reversible loss of one copy of chromosome 5 (Ch5). Here, we explore a hypothesis that more than one gene for negative regulation of echinocandin tolerance is carried on Ch5. We constructed C. albicans strains that each lacked one of the following Ch5 genes: CHT2 for chitinase, PGA4 for glucanosyltransferase, and CSU51, a putative transcription factor. We demonstrate that independent deletion of each of these genes increased tolerance for caspofungin and anidulafungin, another echinocandin. Our data indicate that Ch5 carries multiple genes for negative control of echinocandin tolerance, although the final number has yet to be established.

MeSH terms

  • Anidulafungin
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects*
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • Caspofungin
  • Chitinases / deficiency
  • Chitinases / genetics
  • Chromosome Mapping
  • Chromosomes, Fungal / chemistry*
  • Drug Resistance, Fungal / genetics*
  • Drug Tolerance / genetics*
  • Echinocandins / pharmacology*
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Deletion
  • Glycosyltransferases / deficiency
  • Glycosyltransferases / genetics
  • Humans
  • Lipopeptides / pharmacology*
  • Microbial Sensitivity Tests
  • Transcription Factors / deficiency
  • Transcription Factors / genetics

Substances

  • Antifungal Agents
  • Echinocandins
  • Fungal Proteins
  • Lipopeptides
  • Transcription Factors
  • Anidulafungin
  • Glycosyltransferases
  • Chitinases
  • Caspofungin