Serum repressing efflux pump CDR1 in Candida albicans

The wild-type C. albicans cells (SC5314) but not the cdr1/cdr1 mutant cells became more susceptible to the antifungal drug when the medium contained serum. To understand the regulation of CDR1 in the presence of serum, we have constructed CDR1 promoter-Renilla luciferase (CDR1p-RLUC) reporter to monitor the activity of the CDR1 promoter in C. albicans. As expected, the expression of CDR1p-RLUC was induced by miconazole. Surprisingly, it was repressed by serum. Consistently, the level of CDR1 mRNA was also reduced in the presence of serum but not N-acetyl-D-glucosamine, a known inducer for germ tube formation.Our finding that the expression of CDR1 is repressed by serum raises the question as to how does CDR1 contribute to the drug resistance in C. albicans causing candidemia. This also suggests that it is important to re-assess the prediction of in vivo therapeutic outcome of candidemia based on the results of standard in vitro antifungal susceptibility testing, conducted in the absence of serum.In the past decades, the prevalence of candidemia has increased significantly. Among them, Candida albicans is the most frequently isolated fungal pathogen in humans and has caused morbidity in seriously debilitated and immunocompromised hosts. Coinciding with the increased usage of antifungal drugs, the incidences of drug resistance have also increased [1,2].Overexpression of CDR1, an ATP binding cassette (ABC) transporter, has been shown to be the major mechanism for the drug resistance of clinical isolates [3]. Mutations on CDR1 in C. albicans have resulted in an increased susceptibility to azole drugs [4], which is consistent with the observation that overexpression of CDR1 contributes to the drug resistance of clinical isolates of C. albicans [5]. Interestingly, the expression of CDR1 is increased approximately 4-fold in Catup1/Catup1 mutant cells, which are predominately in the hyphal form [6]. This data suggests that CaTup1 acts as a negative regulator of CDR1. Recent