title: Mechanisms of azole resistance among clinical isolates of Candida glabrata in Poland.
abstract: Candida glabrata is currently ranked as the second most frequently isolated aetiological agent of human fungal infections, next only to Candida albicans. In comparison with C. albicans, C. glabrata shows lower susceptibility to azoles, the most common agents used in treatment of fungal infections. Interestingly, the mechanisms of resistance to azole agents in C. albicans have been much better investigated than those in C. glabrata. The aim of the presented study was to determine the mechanisms of resistance to azoles in 81 C. glabrata clinical isolates from three different hospitals in Poland. The investigation was carried out with a Sensititre Yeast One test and revealed that 18 strains were resistant to fluconazole, and 15 were cross-resistant to all other azoles tested (voriconazole, posaconazole and itraconazole). One isolate resistant to fluconazole was cross-resistant to voriconazole, and resistance to voriconazole only was observed in six other isolates. All strains were found to be susceptible to echinocandins and amphotericin B, and five were classified as resistant to 5-fluorocytosine. The sequence of the ERG11 gene encoding lanosterol 14-α demethylase (the molecular target of azoles) of 41 isolates, including all strains resistant to fluconazole and three resistant only to voriconazole, was determined, and no amino acid substitutions were found. Real-time PCR studies revealed that 13 of 15 azole-resistant strains showed upregulation of the CDR1 gene encoding the efflux pump. No upregulation of expression of the CDR2 or ERG11 gene was observed.
authors.affiliation: Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdansk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Szweda
authors.affiliation: Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdansk, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gucwa
authors.affiliation: Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Romanowska
authors.affiliation: Department of Clinical Microbiology and Immunology, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dzierz Anowska-Fangrat
authors.affiliation: Department of Clinical Microbiology, Hospital of the Medical University of Gdansk, Debinki Str. 7, 80-954 Gdansk, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Naumiuk
authors.affiliation: Department of Microbiology, Faculty of Chemistry, Gdansk University of Technology, Narutowicza Str. 11/12, 80-233 Gdansk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Brillowska-Da Browska
authors.affiliation: Department of Microbiology and Immunology, Pomeranian Medical University, Powstanców Wielkopolskich 72, 70-111 Szczecin, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Wojciechowska-Koszko
authors.affiliation: Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdansk, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Milewski
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D041221:Candida glabrata / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006761:Hospitals; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D011044:Poland; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D000666:Amphotericin B; D003577:Cytochrome P-450 Enzyme System