Molecular aspects of fluconazole resistance development in Candida albicans

• Published in: Mycoses Vol. 42; no. 7-8; pp. 453 - 458
• Main Authors: Franz, Renate, Ruhnke, M., Morschhäuser, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.1999; Blackwell
• Subjects: AIDS-Related Opportunistic Infections - microbiology; AIDS/HIV; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - pharmacology; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - genetics; Candidiasis, Oral - microbiology; Drug Resistance, Microbial - genetics; fluconazole; Fluconazole - pharmacology; Human immunodeficiency virus; Humans; Medical sciences; Pharmacology. Drug treatments; Fungi; Candida albicans; Antifungal agent; Sensitivity resistance; Fluconazole; Triazole derivatives; Fungi Imperfecti; Molecular biology; In vitro; Thallophyta
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1046/j.1439-0507.1999.00498.x

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.