Molecular aspects of fluconazole resistance development in Candida albicans.
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.
Franz
R
R
Zentrum für Infektionsforschung, Universität Würzburg, Germany.
Ruhnke
M
M
Morschhäuser
J
J
D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics*; D002180:Candidiasis, Oral / Q000382:microbiology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans
D000935:Antifungal Agents; D015725:Fluconazole