文献类型：期刊文献

英文题名：Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters

作者：Tong, Yaojun[1,3,10];Liu, Mei[1];Zhang, Yu[4];Liu, Xueting[1];Huang, Ren[4];Song, Fuhang[1];Dai, Huanqin[1];Ren, Biao[1,10];Sun, Nuo[1,9];Pei, Gang[1];Bian, Jiang[1];Jia, Xin-Ming[7];Huang, Guanghua[6];Zhou, Xuyu[1];Li, Shaojie[6];Zhang, Buchang[5];Fukuda, Takashi[11];Tomoda, Hiroshi[12];Omura, Satoshi[11];Cannon, Richard D.[8];Calderone, Richard[9];Zhang, Lixin[1,2,5]

机构：[1]Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark;[4]Guangdong Lab Anim Monitoring Inst, Guangzhou 510260, Guangdong, Peoples R China;[5]Anhui Univ, Inst Hlth Sci, Sch Life Sci, Hefei 230601, Anhui, Peoples R China;[6]Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China;[7]Tongji Univ, Sch Med, Dept Immunol, Shanghai 200092, Peoples R China;[8]Univ Otago, Sir John Walsh Res Inst, Dunedin 9016, New Zealand;[9]Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA;[10]Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[11]Kitasato Univ, Kitasato Inst Life Sci, Res Ctr Trop Dis, Tokyo 1088641, Japan;[12]Kitasato Univ, Grad Sch Pharmaceut Sci, Tokyo 1088641, Japan

年份：2016

卷号：1

期号：3

起止页码：158

外文期刊名：SYNTHETIC AND SYSTEMS BIOTECHNOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000441179800004)】；

基金：This work was supported by the National Program on Key Basic Research Project (973program, 2013CB734000), in part by grants from the National Natural Science Foundation of China [31670052, 31430002, 31320103911, 31400090, 81302678 and 31125002], the Ministry of Science and Tech-nology of the People's Republic of China [2011ZX09102-011-11, 2013ZX10005004-005], China Ocean Mineral Resources R & D Association (Grant No. DY125-15-T-07), and the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312184. YT is partially supported by a grant from the Novo Nordisk Foundation. LZ is an awardee for the National Distinguished Young Scholar Program in China.

语种：英文

外文关键词：Candida albicans; ABC transporter; Beauvericin; Virtual screening; Multi-drug resistance; Synergy

摘要：Multi-drug resistance of pathogenic microorganisms is becoming a serious threat, particularly to immunocompromised populations. The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies. Unfortunately, with traditional drug discovery approaches, only echinocandins was approved by FDA as a new class of antifungals in the past two decades. Drug efflux is one of the major contributors to multi-drug resistance, the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance. In this study, we combined structure-based virtual screening and whole-cell based mechanism study, identified a natural product, beauvericin (BEA) as a drug efflux pump modulator, which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette (ABC) transporters; meantime, BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species (ROS). It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole (KTC) and could cure the murine model of disseminated candidiasis. Toxicity evaluation of BEA, including acute toxicity test, Ames test, and hERG (human ether-a-a-go-go-related gene) test promised that BEA can be harnessed for treatment of candidiasis, especially the candidiasis caused by ABC overexpressed multi-drug resistant C. albicans. (c) 2016 Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).