globalchange  > 气候变化与战略
DOI: 10.1016/j.scib.2020.12.035
Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p
Author: Tong Y.; Zhang J.; Sun N.; Wang X.-M.; Wei Q.; Zhang Y.; Huang R.; Pu Y.; Dai H.; Ren B.; Pei G.; Song F.; Zhu G.; Wang X.; Xia X.; Chen X.; Jiang L.; Wang S.; Ouyang L.; Xie N.; Zhang B.; Jiang Y.; Liu X.; Calderone R.; Bai F.; Zhang L.; Alterovitz G.
Source Publication: Science Bulletin
ISSN: 20959273
Publishing Year: 2021
Language: 英语
keyword in Chinese: Berberine ; Candida albicans ; Drug excretion transporter ; Mitochondria ; Multidrug-resistance
Keyword: Candida ; Mammals ; Yeast ; Drug efflux pumps ; Major facilitator superfamily ; Mitochondrial complex ; Mitochondrial function ; Mitochondrial membrane potential ; Multidrug efflux pumps ; Multidrug resistance ; Multidrug resistants ; Mitochondria
English Abstract: 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 by reversing the function of drug efflux pumps. In the life-threatening fungal pathogen Candida albicans, the major facilitator superfamily (MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading to multidrug resistance. 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 (MST) 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. © 2020 Science China Press
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Document Type: 期刊论文
Appears in Collections:气候变化与战略

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Affiliation: State Key Laboratory of Bioreactor Engineering, and School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China; Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Beijing, 100190, China; Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, 100871, China; Georgetown University Medical Center, Department of Microbiology & Immunology, Washington DC, 20057, United States; Institute of Health Sciences, School of Life Sciences, Anhui University, Hefei, 230601, China; Guangdong Laboratory, Animals Monitoring Institute, Guangzhou, 510260, China; Department of Pharmacology, Second Military Medical University, Shanghai, 200433, China; State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark; Key Biosensor Laboratory of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250013, China; Brigham and Women's Hospital, Boston, MA 02115, United States; National Artificial Intelligence Institute, U.S. Department of Veterans Affairs, Washington DC, 20420, United States

Recommended Citation:
Tong Y.,Zhang J.,Sun N.,et al. Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p[J]. Science Bulletin,2021-01-01
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