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 com...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.展开更多
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)。
文摘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.
