Effects of antifungal agents on the fungal proteome: informing on mechanisms of sensitivity and resistance

Expert Rev Proteomics. 2021 Mar;18(3):185-199. doi: 10.1080/14789450.2021.1912601. Epub 2021 Apr 12.

Abstract

Introduction: Antifungal agents are essential in the fight against serious fungal disease, however emerging resistance is threatening an already limited collection of therapeutics. Proteomic analyses of effects of antifungal agents can expand our understanding of multifactorial mechanisms of action and have also proven valuable to elucidate proteomic changes associated with antifungal resistance.

Areas covered: This review covers the application of proteomic techniques to examine sensitivity and resistance to antifungals including commonly used therapeutics, amphotericin B, echinocandins and the azoles, based predominantly on studies involving Aspergillus fumigatus, Candida albicans and Candida glabrata from the last 10 years. In addition, non-clinical antimicrobial agents are also discussed, which highlight the potential of proteomics to identify new antifungal targets.

Expert commentary: Fungal proteomics has evolved in the last decade with increased genome availability and developments in mass spectrometry. Collectively, these have led to the advancement of proteomic techniques, allowing increased coverage of the proteome. Gel-based proteomics laid the foundation for these types of studies, which has now shifted to the more powerful gel-free proteomics. This has resulted in the identification of key mediators and potential biomarkers of antifungal resistance, as well as elucidating the mechanisms of action of novel and established antifungal agents.

Keywords: Aspergillus; Candida; Fungal proteomics; amphotericin B; antifungal; azole; echinocandin; gliotoxin; resistance.

Publication types

  • Review

MeSH terms

  • Antifungal Agents* / pharmacology
  • Echinocandins
  • Humans
  • Microbial Sensitivity Tests
  • Proteome*
  • Proteomics

Substances

  • Antifungal Agents
  • Echinocandins
  • Proteome