Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element

摘要: Resistance to azole antifungal drugs in clinical isolates of the human fungal pathogen Candida albicans is often caused by constitutive overexpression CDR1 gene, which encodes a multidrug efflux pump ABC transporter superfamily. To understand relevance recently identified negative regulatory element (NRE) promoter for control expression scenario, we investigated effect mutation or deletion NRE on two matched pairs azole-sensitive and resistant C. albicans. Expression GFP lacZ reporter genes from wild type was much higher azole-resistant than azole-susceptible isolates, reflecting known differences these strains. Deletion resulted enhanced gene strains, but did not further increase already high activity In agreement with findings, electrophoretic mobility shift assays showed reduced binding nuclear extracts as compared sensitive isolates. These results demonstrate that involved maintaining at basal levels this repression overcome resulting concomitant drug resistance.