Sanglard D, Ischer F, Bille J; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18; 46 (abstract no. C69).

Institut de Microbiologie, University Hospital Lausanne, Lausanne, Switzerland.

With the increasing use of azole antifungal agents in the treatment of fungal infections, emergence of resistance to these agents has been observed by many investigators. We have used fluconazole resistant C. albicans isolates from AIDS patients with oropharyngeal candidiasis as tools to investigate the molecular basis of resistance to azole antifungal agents. We could show in a recent study that multidrug efflux transporters were playing an important role in the appearance of resistance, but without excluding the involvement of other factors in this phenomenon (see text for references). We analysed therefore in closer details changes in affinity of azole antifungal agents to their cellular target (the cytochrome P450 CYP51A1) as a likely possible factor. A strategy was designed consisting of functional expression of the C. albicans CYP51A1 genes from sequential clinical isolates from patients in Saccharomyces cerevisiae. This selection enabled the detection of mutations in the different cloned CYP51A1 genes affecting selectively the affinity of azole derivatives to their target. We speculate that these specific mutations combine with the effect of multidrug efflux transporters in the clinical isolates, thus probably contributing to different pattern and degree of resistance to azole derivatives.

Publication Types:

• Meeting Abstracts

Keywords:

• Antifungal Agents
• Antigens, Fungal
• Azoles
• Candida albicans
• Candidiasis
• Cytochrome P-450 Enzyme System
• Fluconazole
• Humans
• Membrane Transport Proteins
• Mutation
• Mycoses
• Saccharomyces cerevisiae
• genetics
• immunology
• lanosterol 14 alpha-demethylase

Other ID:

• 98927605

UI: 102234779

From Meeting Abstracts