Molecular basis of resistance to azole antifungals

Trends Mol Med. 2002 Feb;8(2):76-81. doi: 10.1016/s1471-4914(02)02280-3.


The increased incidence of invasive mycoses and the emerging problem of antifungal drug resistance has prompted investigations of the underlying molecular mechanisms, particularly for the azole compounds central to current therapy. The target site for the azoles is the ERG11 gene product, the cytochrome P450 lanosterol 14alpha-demethylase, which is part of the ergosterol biosynthetic pathway. The resulting ergosterol depletion renders fungal cells vulnerable to further membrane damage. Development of azole resistance in fungi may occur through increased levels of the cellular target, upregulation of genes controlling drug efflux, alterations in sterol synthesis and decreased affinity of azoles for the cellular target. Here, we review the adaptative changes in fungi, in particular Candida albicans, in response to inhibitors of ergosterol biosynthesis. The molecular mechanisms of azole resistance might help in devising more effective antifungal therapies.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Azoles / chemistry
  • Azoles / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / metabolism
  • Drug Resistance, Fungal*
  • Ergosterol / biosynthesis
  • Humans
  • Mycoses / drug therapy
  • Polyenes / pharmacology


  • Antifungal Agents
  • Azoles
  • Polyenes
  • Ergosterol