【摘 要】
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Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant patho-gens.The overexpression of drug efflux pumps is one of the major contributors to multidrug resistance(MDR).Reversing the function of drug efflux pumps is
【机 构】
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State Key Laboratory of Bioreactor Engineering and School of Biotechnology,Fast China University of
论文部分内容阅读
Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant patho-gens.The overexpression of drug efflux pumps is one of the major contributors to multidrug resistance(MDR).Reversing the function of drug efflux pumps is a promising approach to overcome MDR.In the life-threatening fungal pathogen Candida albicans,the major facilitator superfamily (MFS) transporter Mdr1p can excrete many structurally unrelated antifungals,leading to MDR.Here we report a counter-intuitive case of reversing MDR in C.albicans by using a natural product berberine to hijack the overex-pressed Mdr1p for its own importation.Moreover,we illustrate that the imported berberine accumulates in mitochondria and compromises the mitochondrial function by impairing mitochondrial membrane potential and mitochondrial Complex I.This results in the selective elimination of Mdr1p overexpressed C.albicans cells.Furthermore,we show that berberine treatment can prolong the mean survival time of mice with blood-borne dissemination of Mdr1p overexpressed multidrug-resistant candidiasis.This study provides a potential direction of novel anti-MDR drug discovery by screening for multidrug efflux pump converters.
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