Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p

• DOI: 10.1016/j.scib.2020.12.035
• Publication Date: 2020-12-31T01:41:16Z
• Authors: Yaojun Tong; Jingyu Zhang; Nuo Sun; Xiang-Ming Wang; Qi Wei; Yu Zhang; Ren Huang; Yingying Pu; Huanqin Dai; Biao Ren; Gang Pei; Fuhang Song; Guoliang Zhu; Xinye Wang; Xuekui Xia; Xiangyin Chen; Lan Jiang; Shenlin Wang; Liming Ouyang; Ning Xie; Buchang Zhang; Yuanying Jiang; Xueting Liu; Richard Calderone; Fan Bai; Lixin Zhang; Gil Alterovitz
• Keywords: Efflux; Major facilitator superfamily

Clinical use of antimicrobials faces great challenges from the emergence multidrug-resistant pathogens. The overexpression drug efflux pumps is one major contributors to multidrug resistance (MDR). Reversing function a promising approach overcome MDR. In life-threatening fungal pathogen Candida albicans, facilitator superfamily (MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading Here we report counterintuitive case reversing MDR in C. albicans by using natural product berberine hijack overexpressed for its own importation. Moreover, illustrate that imported accumulates mitochondria and compromises mitochondrial impairing membrane potential Complex I. This results selective elimination cells. Furthermore, show treatment prolong mean survival time mice with blood-borne dissemination candidiasis. study provides direction novel anti-MDR discovery screening pump converters.