The potential of respiration inhibition as a new approach to combat human fungal pathogens

Curr Genet. 2019 Dec;65(6):1347-1353. doi: 10.1007/s00294-019-01001-w. Epub 2019 Jun 6.

Abstract

The respiratory chain has been proposed as an attractive target for the development of new therapies to tackle human fungal pathogens. This arises from the presence of fungal-specific electron transport chain components and links between respiration and the control of virulence traits in several pathogenic species. However, as the physiological roles of mitochondria remain largely undetermined with respect to pathogenesis, its value as a potential new drug target remains to be determined. The use of respiration inhibitors as fungicides is well developed but has been hampered by the emergence of rapid resistance to current inhibitors. In addition, recent data suggest that adaptation of the human fungal pathogen, Candida albicans, to respiration inhibitors can enhance virulence traits such as yeast-to-hypha transition and cell wall organisation. We conclude that although respiration holds promise as a target for the development of new therapies to treat human fungal infections, we require a more detailed understanding of the role that mitochondria play in stress adaption and virulence.

Keywords: Candida; Metabolism; Mitochondria; Respiration; Respirometry; Yeast.

Publication types

  • Review

MeSH terms

  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candida albicans / pathogenicity
  • Drug Therapy, Combination
  • Electron Transport Complex I / drug effects
  • Electron Transport Complex I / metabolism
  • Electron Transport Complex II / drug effects
  • Electron Transport Complex II / metabolism
  • Electron Transport Complex III / drug effects
  • Electron Transport Complex III / metabolism
  • Electron Transport Complex IV / drug effects
  • Electron Transport Complex IV / metabolism
  • Fungi / drug effects
  • Fungi / metabolism
  • Fungi / pathogenicity
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mycoses / drug therapy
  • Oxidoreductases / drug effects
  • Oxidoreductases / metabolism
  • Virulence / drug effects

Substances

  • Antifungal Agents
  • Oxidoreductases
  • duroquinol oxidase
  • Electron Transport Complex II
  • Electron Transport Complex IV
  • Electron Transport Complex I
  • Electron Transport Complex III