Investigation into the molecular mechanisms of itraconazole resistance in Candida dubliniensis

Abstract

Candida dubliniensis is a recently identified yeast species primarily associated with oral carriage and infection in HIV-infected individuals. Previous studies have shown that only a small number of clinical isolates are resistant to the commonly used antifungal drug fluconazole and that stable resistance to fluconazole can be induced in vitro in this species. Overexpression of the multidrug resistance gene CdMDR1 has previously been shown to be a major contributor to resistance in fluconazole-resistant isolates and in vitro-generated derivatives. However, given the inability of CdMdr1p to mediate the transport of other azole drugs such as itraconazole and the high prevalence of nonsense mutations in the multidrug resistance gene CdCDR1, the general aim of the present study was to investigate the prevalence and molecular basis of itraconazole resistance in C. dubliniensis.