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beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters

Synthetic and Systems Biotechnology 2016年第3期1卷 158-168页

作者： Yaojun Tong Mei Liu Yu Zhang Xueting Liu Ren Huang Fuhang Song Huanqin Dai Biao Ren Nuo Sun Gang Pei Jiang Bian Xin-Ming Jia Guanghua Huang Xuyu Zhou Shaojie Li Buchang Zhang Takashi Fukuda Hiroshi Tomoda SatoshiOmura Richard DCannon Richard Calderone Lixin Zhang CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 200237China The Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKgs.Lyngby2800Denmark Guangdong Laboratory Animals Monitoring Institute Guangzhou 510260China Institute of Health Sciences School of Life SciencesAnhui UniversityHefei 230601China State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Department of Immunology School of MedicineTongji UniversityShanghai 200092China Sir John Walsh Research Institute University of OtagoDunedin 9016New Zealand Department of Microbiology&Immunology Georgetown University Medical CenterWashingtonDC 20057US University of Chinese Academy of Sciences Beijing 100049China Research Center for Tropical Diseases Kitasato Institute for Life SciencesKitasato UniversityTokyo 108-8641Japan Graduate School of Pharmaceutical Sciences Kitasato UniversityTokyo 108-8641Japan

Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,particularly to immunocompromised *** high mortality of systematic fungal infections necessitates novel antifungal drugs and ***,with traditional drug discovery approaches,only echinocandins was approved by FDA as a new class of antifungals in the past two *** 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 *** 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 *** evaluation of BEA,including acute toxicity test,Ames test,and hERG(human ether-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 ***.

关键词： Candida albicans ABC transporter beauvericin Virtual screening Multi-drug resistance Synergy

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beauvericin production by the Lepidoptera pathogenic fungus Isaria tenuipes: Analysis of natural specimens, synnemata from cultivation, and mycelia from liquid-media fermentation

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Natural Products and Bioprospecting 2011年第3期1卷 112-115页

作者： Sumalee SUPOTHINA Urarat SRISANOH Sutichai NITHITHANASILP Kanoksri TASANATHAI J.Jennifer LUANGSA-ARD Chun-Ru LI Masahiko ISAKA National Center for Genetic Engineering and Biotechnology(BIOTEC) 113 Thailand Science ParkPhaholyothin RoadKlong LuangPathumthani 12120Thailand Anhui Provincial Key Laboratory for Microbial Control Anhui Agricultural UniversityHefei 230036AnhuiChina

beauvericin was analyzed in three forms of the Lepidoptra pathogenic fungus Isaria tenuipes(4 isolates):(a)natural specimen,(b)cultivated synnemata on rice media,and(c)mycelia from fermentation in liquid *** was detected in very low amounts in all tested natural *** on rice contained much higher concentrations of beauvericin than the corresponding natural materials,although the concentrations were lower than mycelia from liquid *** results casted a caution that beauvericin concentration should be carefully checked,as a possible toxic constituent,upon mass production of a selected strain of Isaria tenuipes for health food purposes.

关键词： beauvericin Isaria tenuipes chemotaxonomy toxin

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