Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalScience China Life Sciences
DOIs
StateAccepted/In press - 2022

Keywords

  • Gram-negative pathogens
  • P. multocida
  • citrate synthase
  • citric acid
  • melatonin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

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