Understanding fluconazole tolerance in Candida albicans: implications for effective treatment of candidiasis and combating invasive fungal infections

J Glob Antimicrob Resist. 2023 Dec:35:314-321. doi: 10.1016/j.jgar.2023.10.019. Epub 2023 Nov 2.

Abstract

Objectives: Fluconazole (FLC) tolerant phenotypes in Candida species contribute to persistent candidemia and the emergence of FLC resistance. Therefore, making FLC fungicidal and eliminating FLC tolerance are important for treating invasive fungal diseases (IFDs) caused by Candida species. However, the mechanisms of FLC tolerance in Candida species remain to be fully explored.

Methods: This review discusses the high incidence of FLC tolerance in Candida species and the importance of successfully clearing FLC tolerance in treating candidiasis. We further define and characterize FLC tolerance in C. albicans.

Results: This review identifies global factors affecting FLC tolerance and suggest that FLC tolerance is a strategy of C. albicans response to FLC damage whose mechanism differs from FLC resistance.

Conclusions: This review highlights the significance of the cell membrane and cell wall integrity in FLC tolerance, guiding approaches to combat IFDs caused by Candida species..

Keywords: Candida albicans; Fluconazole synergistic lethal adjuvants; Fluconazole synergistic lethal targets; Fluconazole tolerance; Invasive fungal disease.

Publication types

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

MeSH terms

  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Candida
  • Candida albicans
  • Candidiasis* / drug therapy
  • Candidiasis* / microbiology
  • Fluconazole* / pharmacology
  • Fluconazole* / therapeutic use
  • Humans

Substances

  • Fluconazole
  • Antifungal Agents