Molecular Evolution of Antifungal Drug Resistance

Annu Rev Microbiol. 2017 Sep 8;71:753-775. doi: 10.1146/annurev-micro-030117-020345.

Abstract

The fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus have transitioned from a rare curiosity to a leading cause of human mortality. The management of infections caused by these organisms is intimately dependent on the efficacy of antifungal agents; however, fungi that are resistant to these treatments are regularly isolated in the clinic, impeding our ability to control infections. Given the significant impact fungal pathogens have on human health, it is imperative to understand the molecular mechanisms that govern antifungal drug resistance. This review describes our current knowledge of the mechanisms by which antifungal drug resistance evolves in experimental populations and clinical settings. We explore current antifungal treatment options and discuss promising strategies to impede the evolution of drug resistance. By tackling antifungal drug resistance as an evolutionary problem, there is potential to improve the utility of current treatments and accelerate the development of novel therapeutic strategies.

Keywords: antifungal; evolution; fitness; fungal pathogen; resistance; stress responses.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Aspergillus fumigatus / drug effects*
  • Aspergillus fumigatus / genetics
  • Aspergillus fumigatus / isolation & purification
  • Candida albicans / drug effects*
  • Candida albicans / genetics
  • Candida albicans / isolation & purification
  • Cryptococcus neoformans / drug effects*
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / isolation & purification
  • Drug Resistance, Fungal*
  • Evolution, Molecular*
  • Humans
  • Mycoses / drug therapy
  • Mycoses / microbiology

Substances

  • Antifungal Agents