Molecular Aspects of Fluconazole Resistance Development in Candida Albicans

Mycoses. 1999;42(7-8):453-8. doi: 10.1046/j.1439-0507.1999.00498.x.

Abstract

Serial Candida albicans isolates from recurrent episodes of oropharyngeal candidosis (OPC) in four AIDS patients which became fluconazole-resistant during therapy were analysed by molecular methods. The CARE-2 fingerprint patterns of the isolates demonstrated that in all four patients fluconazole resistance developed in a previously more susceptible strain. In two cases resistance correlated with enhanced expression of genes encoding multiple drug resistance proteins that mediate active drug efflux. Enhanced mRNA levels of the CDR1/CDR2 genes encoding ABC transporters were observed in fluconazole-resistant isolates from one patient compared with the corresponding susceptible isolates. The fluconazole-resistant isolates from another patient exhibited high mRNA levels of the MDR1 gene encoding a membrane transport protein of the major facilitator superfamily that was not detectably expressed in any of the fluconazole-susceptible isolates. These results demonstrate that in AIDS patients with recurrent OPC the development of fluconazole resistance is usually caused by molecular changes in a previously susceptible C. albicans strain from the same patient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / microbiology
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / genetics*
  • Candidiasis, Oral / microbiology*
  • Drug Resistance, Microbial / genetics
  • Fluconazole / pharmacology*
  • Humans

Substances

  • Antifungal Agents
  • Fluconazole