Antifungal resistance in Aspergillus terreus: A current scenario

Fungal Genet Biol. 2019 Oct:131:103247. doi: 10.1016/j.fgb.2019.103247. Epub 2019 Jun 25.

Abstract

Invasive aspergillosis caused by intrinsically resistant non-fumigatus Aspergillus species displays a poor outcome in immunocompromised patients. The polyene antifungal amphotericin B (AmB) remains to be "gold standard" in the treatment of invasive fungal infections. Aspergillus terreus is innately resistant to AmB, in vivo and in vitro. Till now, the exact mode of action in polyene resistance is not well understood. This review highlights the underlying molecular basis of AmB resistance in A. terreus, displaying data obtained from AmB susceptible A. terreus and AmB resistant A. terreus strains. The effect of AmB on main cellular and molecular functions such as fungal respiration and stress response pathways will be discussed in detail and resistance mechanisms will be highlighted. The fungal stress response machinery seems to be a major player in the onset of AmB resistance in A. terreus.

Keywords: AMB-resistance; Aspergillus terreus; Invasive Aspergillosis; Resistance mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphotericin B / metabolism
  • Amphotericin B / therapeutic use*
  • Animals
  • Antifungal Agents / metabolism
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / drug therapy*
  • Aspergillosis / metabolism
  • Aspergillosis / microbiology
  • Aspergillus / drug effects*
  • Aspergillus / metabolism
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Drug Resistance, Fungal / physiology*
  • Ergosterol / metabolism
  • Heat-Shock Proteins / metabolism
  • Humans
  • Lipid Bilayers / metabolism
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Polyenes / metabolism
  • Polyenes / therapeutic use*

Substances

  • Antifungal Agents
  • Heat-Shock Proteins
  • Lipid Bilayers
  • Polyenes
  • Amphotericin B
  • Ergosterol