Analysis of Molecular Resistance Mechanisms of Itraconazole in Candida Albicans Clinical Isolates from India

Opportunistic fungal infections resistant to antifungal agents have been increasingly documented in recent years and their frequency will likely continue to increase. This phenomenon appears due largely to the extensive use of antifungal agents to treat fungal infections that typically occur in severely immunocompromised and/or critically ill patients. Candida species are leading fungi responsible for these invasive infections. In this study, we describe resistance mechanisms in Itraconazole-resistant isolates of Candida albicans isolated from AIDS patients. These mechanisms include the presence of point mutations in the ERG11 gene and overexpression of ERG11, and several genes encoding efflux pumps, as measured by quantitative real-time reverse transcriptase polymerase chain reaction. Several fluconazole-resistant strains had multiple mechanisms of resistance. Four mutations previously described, Y132F, K143R, E266D, and V437I, were identified among the strains, whereas some isolates contained more than one mutation. Fourteen novel mutations were identified. Interestingly, all Itraconazole-resistant isolates showed homozygosity at mating-type loci (MTL) associated with Itraconazole resistance.