Identification of efflux inhibitors through a drug repurposing strategy in Candida albicans
Abstract
Introduction Candida albicans is a major cause of nosocomial fungal infections, often associated with high morbidity and mortality. The rising resistance to antifungal drugs, particularly azoles, underscores the need for new therapeutic strategies. Among resistance mechanisms, alterations in drug targets and overexpression of efflux pump genes play key roles. Efflux inhibitors can enhance the intracellular drug accumulation, thereby restoring antifungal efficacy and preventing resistance development. Drug repurposing offers a cost-effective and time-efficient alternative for identifying new drugs, including efflux inhibitors. In this study, we used an in silico drug repurposing approach to identify approved drugs associated with membrane transport functions and evaluate their efflux-modulating potential in vitro . Methods Using the DrugBank database, we screened predicted membrane transport proteins in C. albicans and selected those with homology to known drug targets. A subset of drugs, representative of each chemical group, was selected for in vitro screening against the reference strain C. albicans ATCC 90028. We further evaluated the potential adjuvant effect of these drugs on the activity of fluconazole. Finally, the efflux inhibitory effect of the candidate drugs was assessed by real-time fluorometric detection of ethidium bromide accumulation. Results A total of 245 predicted membrane transport proteins were screened, 51 of which showed homology to known drug targets…
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