title: [Investigation of mutations in transcription factors of efflux pump genes in fluconazole-resistant Candida albicans strains overexpressing the efflux pumps].
abstract: In recent years, a significant rise in the number of immunocompromised patients have been observed due to cancer chemotherapy, organ transplantation and HIV infection. As a result of this, the frequency of Candida albicans infections in the clinics have been increased. Fluconazole, as being a well tolerated, easy to use drug with minor side effects, is often the first choice antifungal agent for this patient group, both for therapy and prophylaxis. Especially the long-term use of this drug, causes the selection of resistant strains and leads to the development of fluconazole resistance. The most frequently observed resistance mechanism against fluconazole in C.albicans strains is the transportation of the drug out of the cell via efflux pumps. The efflux pumps mainly involved are Cdr1, Cdr2 ve Mdr1 encoded by CDR1, CDR2 and MDR1 genes. It has been shown that, the overexpression of these efflux pump genes was caused by functional mutations in TAC1 and MRR1 genes which encode the transcription factors Tac1p and Mrr1p. This study was aimed to analyze TAC1 and MRR1 genes of 15 C.albicans strains which consist of six fluconazole-susceptible, four susceptible with trailing effect and five fluconazole-resistant isolates plus one resistant strain (DSY292), known to overexpress Mdr1 efflux pump due to P683H mutation in MRR1 gene and one fluconazole-sensitive ATCC 14053 C.albicans strain in terms of mutations with polymerase chain reaction and sequence analysis. Two of the fluconazole-resistant isolates which had overexpression of Cdr1 and Cdr2 pumps known to have overexpression of TAC1 gene, revealed R673Q and A736V mutations. A P683H point mutation, that overexpressed the Mdr1 pump was detected in a fluconazole-resistant strain, which was known to cause MRR1 overexpression. In conclusion, mutations in the transcription factors of the efflux pump genes may play an important role in the resistance against fluconazole among our selected C.albicans strains.
authors.affiliation: Çankırı State Hospital, Microbiology Laboratory, Çankırı, Turkey. tkalkandelen@hotmail.com.
authors.forename: Kemal Turan
authors.initials: KT
authors.lastname: Kalkandelen
authors.forename: Mine
authors.initials: M
authors.lastname: Doluca Dereli
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics*; D025141:Drug Resistance, Fungal / Q000235:genetics; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D014157:Transcription Factors; D015725:Fluconazole