文献类型：期刊文献

英文题名：Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p

作者：Tong, Yaojun[1,2,3,10];Zhang, Jingyu[1,2];Sun, Nuo[5];Wang, Xiang-Ming[4];Wei, Qi[3];Zhang, Yu[7];Huang, Ren[7];Pu, Yingying[4];Dai, Huanqin[3,9];Ren, Biao[3];Pei, Gang[3];Song, Fuhang[3];Zhu, Guoliang[1,2];Wang, Xinye[1,2];Xia, Xuekui[11];Chen, Xiangyin[1,2];Jiang, Lan[1,2];Wang, Shenlin[1,2];Ouyang, Liming[1,2];Xie, Ning[12];Zhang, Buchang[6];Jiang, Yuanying[8];Liu, Xueting[1,2];Calderone, Richard[5];Bai, Fan[4];Zhang, Lixin[1,2];Alterovitz, Gil[12,13]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Key Lab Pathogen Microbiol & Immunol, Inst Microbiol, Beijing 100190, Peoples R China;[4]Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Sch Life Sci, Beijing 100871, Peoples R China;[5]Georgetown Univ, Dept Microbiol & Immunol, Med Ctr, Washington, DC 20057 USA;[6]Anhui Univ, Sch Life Sci, Inst Hlth Sci, Hefei 230601, Peoples R China;[7]Guangdong Lab Anim Monitoring Inst, Guangdong Prov Key Lab Lab Anim, Guangzhou 510663, Peoples R China;[8]Second Mil Med Univ, Dept Pharmacol, Shanghai 200433, Peoples R China;[9]Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China;[10]Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark;[11]Shandong Acad Sci, Biol Inst, Key Biosensor Lab Shandong Prov, Qilu Univ Technol, Jinan 250013, Peoples R China;[12]Brigham & Womens Hosp, Boston, MA 02115 USA;[13]US Dept Vet Affairs, Natl Artificial Intelligence Inst, Washington, DC 20420 USA

年份：2021

卷号：66

期号：18

起止页码：1895

外文期刊名：SCIENCE BULLETIN

收录：;EI(收录号：20210509844410);WOS:【SCI-EXPANDED(收录号:WOS:000692530800012)】；

基金：We thank Joachim Morschhauser, Dominique Sanglard, and Theodore White for kindly providing drug-resistant clinical fungal isolates. We thank Haian Fu, Bruce Alberts, Rong An, Elizabeth Ashforth, and Glen Bulmer for their critical reading of the manuscript and helpful discussions. This work was supported by the National Key Research and Development Program of China (2020YFA0907800), the National Natural Science Foundation of China (31720103901), the "111"Project of China (B18022), the Fundamental Research Funds for the Central Universities (22221818014S), the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, the Shandong Taishan Scholar Award, and the Novo Nordisk Foundation (NNF10CC1016517).

语种：英文

外文关键词：Candida albicans; Berberine; Multidrug-resistance; Drug excretion transporter; Mitochondria

摘要：Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant pathogens. 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 counterintuitive case of reversing MDR in C. albicans by using a natural product berberine to hijack the overexpressed 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. (c) 2020 Science China Press. Published by Elsevier B.V. and Science China Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).