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Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates

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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 Candida dubliniensis, 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.

Keywords: Candida dubliniensis; Cdr1p; Cdr2p; analyse des stérols; effet résiduel; fluconazole resistance; résistance au fluconazole; sterol analysis; trailing effect

Document Type: Research Article

DOI: http://dx.doi.org/10.1139/w11-025

Affiliations: 1: Comenius University in Bratislava, Faculty of Natural Sciences, Department of Microbiology and Virology, Mlynská dolina B-2, 842 15 Bratislava, Slovak Republic. 2: Microbiology Research Unit, Division of Oral Biosciences, School of Dental Science and Dublin Dental Hospital, University of Dublin, Trinity College, Dublin 2, Republic of Ireland. 3: Medical University Vienna, Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria. 4: Chemical Institute, Faculty of Natural Sciences, Comenius University, Mlynská dolina CH-2, 842 15 Bratislava, Slovak Republic.

Publication date: May 4, 2011

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  • Published since 1954, this monthly journal contains new research in the field of microbiology including applied microbiology and biotechnology; microbial structure and function; fungi and other eucaryotic protists; infection and immunity; microbial ecology; physiology, metabolism and enzymology; and virology, genetics, and molecular biology. It also publishes review articles and notes on an occasional basis, contributed by recognized scientists worldwide.
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