Calabrese DC, Bille J, Barchiesi F, Sanglard D; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1998 Sep 24-27; 38: 112 (abstract no. C-152).

Institute of Microbiology, University Hospital, Lausanne, Switzerland.

From a yeast strain collection from HIV+ -patients with OPC, 66 C. albicans matched isolates with decreased susceptibility to azole antifungal agents originating from 19 patients were analysed for mechanisms of resistance to azole antifungal agents. Overexpression of the ABC-transporter genes CDR1 and CDR2 were found in 20 azole-resistant clinical isolates from 7 patients and overexpression of the Major Facilitator gene MDR1 was found in 9 azole-resistant isolates from 6 patients. Overexpression of multidrug transporter genes from both families was found in 1 isolate. Alterations of the target of azoles (CYP51A1) were investigated by RFLP-PCR and at least the following known amino acid substitutions were found : R467K was present on both CYP51A1 alleles in 1 azole-resistant isolates from 1 patient which also overexpressed CDR1 and CDR2, S405F on both CYP51A1 alleles of 2 azole-resistant isolates from 2 patients combined in one with overexpression of MDR1 and in the other with an additional Y132H substitution, G464S on both CYP51A1 alleles of 4 azole-resistant isolates from 2 patients with no paralleled overexpression of multidrug transporters. Other still unknown mutations in CYP51A1 may be present in the CYP51A1 genes of these C. albicans isolates. Although azole resistance of 5 isolates from 2 patients could not be correlated neither with multidrug transporters-mediated mechanisms nor with known substitutions in CYP51A1 contributing to azole resistance, these results suggest that multiple combinations of mechanisms exist for the development of azole resistance in C. albicans. Multidrug transporter genes from C. glabrata, C. tropicalis or C. krusei have been isolated from these organisms and preliminary results of the expression of these genes in the azole-resistant isolates of these yeast species will be presented.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• ATP-Binding Cassette Transporters
• Acquired Immunodeficiency Syndrome
• Antifungal Agents
• Azoles
• Candida
• Candidiasis
• Case-Control Studies
• HIV Infections
• HIV Seropositivity
• Humans
• Membrane Transport Proteins
• Saccharomyces cerevisiae

Other ID:

• 20710700

UI: 102188000

From Meeting Abstracts