Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates.

Hdl Handle:
http://hdl.handle.net/10147/221873
Title:
Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates.
Authors:
Borecká, Silvia; Pinjon, Emmanuelle; Sullivan, Derek J; Kuchler, Karl; Blaško, Jaroslav; Kulková, Naďa; Bujdáková, Helena
Affiliation:
Comenius University in Bratislava, Department of Microbiology and Virology, Mlynská dolina, Bratislava, Slovak Republic.
Citation:
Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates. 2011, 57 (5):416-26 Can. J. Microbiol.
Journal:
Canadian journal of microbiology
Issue Date:
May-2011
URI:
http://hdl.handle.net/10147/221873
DOI:
10.1139/w11-025
PubMed ID:
21542785
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.
Item Type:
Article
Language:
en
MeSH:
Antifungal Agents; Candida; Cell Membrane; DNA, Ribosomal Spacer; Drug Resistance, Fungal; Ergosterol; Fluconazole; Fungal Proteins; Genes, Fungal; Genotyping Techniques; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests
ISSN:
1480-3275

Full metadata record

DC FieldValue Language
dc.contributor.authorBorecká, Silviaen_GB
dc.contributor.authorPinjon, Emmanuelleen_GB
dc.contributor.authorSullivan, Derek Jen_GB
dc.contributor.authorKuchler, Karlen_GB
dc.contributor.authorBlaško, Jaroslaven_GB
dc.contributor.authorKulková, Naďaen_GB
dc.contributor.authorBujdáková, Helenaen_GB
dc.date.accessioned2012-05-03T14:39:46Z-
dc.date.available2012-05-03T14:39:46Z-
dc.date.issued2011-05-
dc.identifier.citationCdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates. 2011, 57 (5):416-26 Can. J. Microbiol.en_GB
dc.identifier.issn1480-3275-
dc.identifier.pmid21542785-
dc.identifier.doi10.1139/w11-025-
dc.identifier.urihttp://hdl.handle.net/10147/221873-
dc.description.abstractThe 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Canadian journal of microbiologyen_GB
dc.subject.meshAntifungal Agents-
dc.subject.meshCandida-
dc.subject.meshCell Membrane-
dc.subject.meshDNA, Ribosomal Spacer-
dc.subject.meshDrug Resistance, Fungal-
dc.subject.meshErgosterol-
dc.subject.meshFluconazole-
dc.subject.meshFungal Proteins-
dc.subject.meshGenes, Fungal-
dc.subject.meshGenotyping Techniques-
dc.subject.meshHumans-
dc.subject.meshMembrane Transport Proteins-
dc.subject.meshMicrobial Sensitivity Tests-
dc.titleCdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates.en_GB
dc.typeArticleen
dc.contributor.departmentComenius University in Bratislava, Department of Microbiology and Virology, Mlynská dolina, Bratislava, Slovak Republic.en_GB
dc.identifier.journalCanadian journal of microbiologyen_GB
dc.description.provinceLeinsteren

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