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 

机构地区：[1]College of Veterinary Medicine,Southwest University,Chongqing 400715,China [2]State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources,Guangdong Laboratory of Lingnan Modern Agriculture,Guangdong Provincial Key Laboratory of Animal Nutrition Control,National Engineering Research Center for Breeding Swine Industry,College of Animal Science,South China Agricultural University,Guangzhou 510642,China [3]Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China,Jiangsu Co-innovation Center for Important Animal Infectious Diseases and Zoonoses,College of Veterinary Medicine,Institute of Comparative Medicine,Yangzhou University,Yangzhou 225009,China [4]Johann Friedrich Blumenbach Institute of Zoology and Anthropology,University of Göttingen,Göttingen 37073,Germany [5]Department of Cellular and Structural Biology,University of Texas Health Science Center,San Antonio,TX 78229,USA

出　　处：《Science China(Life Sciences)》2022年第7期1430-1444,共15页中国科学（生命科学英文版）

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)。

摘　　要：Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health worldwide.Despite the urgent need for new antibiotics that effectively fight against pathogenic bacteria,very few compounds are currently under development or approved in the clinical setting.Repurposing compounds for other uses offers a productive strategy for the development of new antibiotics.Here we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during infection.Mechanistically,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 multocida.These 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.

关 键 词：citrate synthase citric acid Gram-negative pathogens MELATONIN P.multocida 

分 类 号：S852.61[农业科学—基础兽医学]