Cdr2p contributes to fluconazole resistance in Candida dubliniensis clinical isolates
| Autor: | Naďa Kulková, Jaroslav Blaško, Emmanuelle Pinjon, Derek J. Sullivan, Helena Bujdáková, Karl Kuchler, Silvia Borecka |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Antifungal Agents
Genotyping Techniques Genes Fungal Immunology ATP-binding cassette transporter Microbial Sensitivity Tests Applied Microbiology and Biotechnology Microbiology Fungal Proteins chemistry.chemical_compound Drug Resistance Fungal Ergosterol DNA Ribosomal Spacer Genetics medicine Humans Fluconazole Molecular Biology Candida chemistry.chemical_classification Fungal protein biology Lanosterol Cell Membrane Membrane Transport Proteins General Medicine biology.organism_classification Sterol chemistry Azole Candida dubliniensis medicine.drug |
| Zdroj: | Canadian Journal of Microbiology. 57:416-426 |
| ISSN: | 1480-3275 0008-4166 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|