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- Title
Cdr2p contributes to fluconazole resistance in clinical isolates.
- Authors
Borecká, Silvia; Pinjon, Emmanuelle; Sullivan, Derek J.; Kuchler, Karl; Blaško, Jaroslav; Kulková, Naďa; Bujdáková, Helena
- Abstract
The development of resistance to azole antifungals used in the treatment of fungal infections can be a serious medical problem. Here, we investigate the molecular mechanisms associated with reduced susceptibility to fluconazole in clinical isolates of , showing evidence of the trailing growth phenomenon. The changes in membrane sterol composition were studied in the presence of subinhibitory fluconazole concentrations. Despite lanosterol and eburicol accumulating as the most prevalent sterols after fluconazole treatment, these ergosterol precursors still support growth of Candida isolates. The overexpression of ABC transporters was demonstrated by immunoblotting employing specific antibodies against Cdr1p and Cdr2p. The presence of a full-length 170 kDa protein Cdr1p was detected in two isolates, while a truncated form of Cdr1p with the molecular mass of 85 kDa was observed in isolate 966/3(2). Notably, Cdr2p was detected in this isolate, and the expression of this transporter was modulated by subinhibitory concentrations of fluconazole. These results suggest that C. dubliniensis can display the trailing growth phenomenon, and such isolates express similar molecular mechanisms like that of fluconazole-resistant isolates and can therefore be associated with recurrent infections.
- Subjects
AZOLES; ANTIFUNGAL agents; COMMUNICABLE disease treatment; MYCOSES; GENETICS of disease susceptibility; GENE expression; CANDIDA; STEROLS; DRUG resistance in microorganisms
- Publication
Canadian Journal of Microbiology, 2011, Vol 57, Issue 5, p416
- ISSN
0008-4166
- Publication type
Article
- DOI
10.1139/w11-025