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Molecular aspects of fluconazole resistance development in Candida albicans

R Franz1, M Ruhnke, J Morschhäuser

  • 1Zentrum für Infektionsforschung, Universität Würzburg, Germany.

Mycoses
|November 5, 1999
PubMed

Insights

In AIDS patients with recurrent oropharyngeal candidosis, fluconazole resistance in Candida albicans often develops from susceptible strains within the same patient. This resistance is linked to increased expression of drug efflux pump genes.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Recurrent oropharyngeal candidosis (OPC) in AIDS patients can lead to antifungal resistance.
  • Candida albicans is a common opportunistic pathogen in immunocompromised individuals.

Purpose of the Study:

  • To investigate the molecular mechanisms of fluconazole resistance development in serial Candida albicans isolates from AIDS patients with recurrent OPC.
  • To determine if resistance emerges from pre-existing susceptible strains within the same patient.

Main Methods:

  • Molecular analysis of serial Candida albicans isolates using CARE-2 fingerprinting.
  • Quantitative analysis of gene expression, specifically focusing on genes encoding multidrug resistance proteins (e.g., CDR1/CDR2, MDR1).

Main Results:

  • Fluconazole resistance developed in previously susceptible Candida albicans strains in all four analyzed AIDS patients.
  • Enhanced expression of multidrug resistance genes (CDR1/CDR2, MDR1) was observed in resistant isolates, correlating with active drug efflux.
  • MDR1 gene expression was significantly higher in resistant isolates from one patient compared to susceptible ones.

Conclusions:

  • Development of fluconazole resistance in AIDS patients with recurrent OPC is typically due to molecular alterations in the patient's own Candida albicans strain.
  • Upregulation of drug efflux pump genes is a key mechanism contributing to fluconazole resistance in these clinical settings.

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