Resistance mechanisms in fluconazole-resistant Candida albicans isolates from vaginal candidiasis.
Candida albicans is the most frequently identified yeast species causing mycotic vaginitis. A significant number of vaginal yeast isolates are resistant to azole antifungal agents in vitro. Here we investigated the molecular mechanisms of resistance in 22 randomly selected fluconazole-resistant vaginal C. albicans isolates. Twelve isolates in this collection were found to be cross-resistant to itraconazole and 15 to voriconazole. Most of them also displayed decreased susceptibility to terbinafine. Northern blot analyses revealed overexpression of the MDR1 gene in all isolates, which in some isolates was accompanied by elevated levels of CDR1/CDR2 and ERG11 expression. Sequence analysis of the polymerase chain reaction-amplified ERG11 gene of selected azole-resistant isolates identified D116E and V488I amino acid alterations in Erg11p that are known to be conserved in fluconazole-resistant strains. The results demonstrate that decreased susceptibilities of vaginal yeast isolates to clinically used azole derivatives are the result of a combination of several molecular mechanisms involving drug efflux and alterations in the structure or cellular amount of 14-alpha-lanosterol demethylase.
Cernicka
Jana
J
Comenius University in Bratislava, Faculty of Natural Sciences, Department of Microbiology and Virology, Mlynska dolina B-2, 842 15 Bratislava 4, Slovak Republic.
Subik
Julius
J
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D002181:Candidiasis, Vulvovaginal / Q000382:microbiology*; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D006801:Humans
D000935:Antifungal Agents; D005656:Fungal Proteins; D015725:Fluconazole