Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

作     者：Fang He Yuan Liu Pan Li Xiaoyan Wu Yaoyao Xia Dong Zhang Nengzhang Li Yuanyi Peng Guoqiang Zhu Rüdiger Hardeland Russel JReiter Wenkai Ren Fang He;Yuan Liu;Pan Li;Xiaoyan Wu;Yaoyao Xia;Dong Zhang;Nengzhang Li;Yuanyi Peng;Guoqiang Zhu;Rüdiger Hardeland;Russel J.Reiter;Wenkai Ren

作者机构：College of Veterinary MedicineSouthwest UniversityChongqing 400715China State Key Laboratory for Conservation and Utilization of Subtropical Agro-BioresourcesGuangdong Laboratory of Lingnan Modern AgricultureGuangdong Provincial Key Laboratory of Animal Nutrition ControlNational Engineering Research Center for Breeding Swine IndustryCollege of Animal ScienceSouth China Agricultural UniversityGuangzhou 510642China Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of ChinaJiangsu Co-innovation Center for Important Animal Infectious Diseases and ZoonosesCollege of Veterinary MedicineInstitute of Comparative MedicineYangzhou UniversityYangzhou 225009China Johann Friedrich Blumenbach Institute of Zoology and AnthropologyUniversity of GöttingenGöttingen 37073Germany Department of Cellular and Structural BiologyUniversity of Texas Health Science CenterSan AntonioTX 78229USA 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2022年第65卷第7期

页      面：1430-1444页

核心收录：

学科分类：0710[理学-生物学] 090601[农学-基础兽医学] 09[农学] 0906[农学-兽医学] 

基　　金：supported by China Agriculture Research System of MOF and MARA(Beef/Yak Cattle,CARS-37) the National Natural Science Foundation of China(31922079,31872365 and 31790411) Chongqing Science&Technology Commission(cstc2017shmszdyfx0036,cstc2017jcyjAX0288) 

主　　题：citrate synthase citric acid Gram-negative pathogens melatonin P.multocida 

摘      要：Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health *** the urgent need for new antibiotics that effectively fight against pathogenic bacteria,very few compounds are currently under development or approved in the clinical *** compounds for other uses offers a productive strategy for the development of new *** we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during ***,melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300,D363,and H265 sites,particularly for the notorious Pasteurella *** findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.