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Melatonin inhibits Gram-negative pathogens by targeting citrate synthase |
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| Authors: | He Fang Liu Yuan Li Pan Wu Xiaoyan Xia Yaoyao Zhang Dong Li Nengzhang Peng Yuanyi Zhu Guoqiang Hardeland Rüdiger Reiter Russel J. Ren Wenkai |
| Affiliation: | 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 G?ttingen, G?ttingen, 37073, Germany ;5.Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, 78229, USA ; |
| Abstract: | 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. |
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