期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 53, 期 4, 页码 442-448出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2018.11.016
关键词
Lipopolysaccharide; Escherichia coli; LptA-LptC interaction; Yeast two-hybrid; Antibacterial agent
资金
- State Mega Programs [2018ZX09711001-007, 2014ZX09507-009-005]
- Beijing Municipal Science and Technology Project [Z141102004414065]
- CAMS Initiative for Innovative Medicine [2016-12M-3-014]
- Foundation for Innovative Research Groups, Joint Research Fund for Overseas Chinese Scholars and Scholars in Hong Kong and Macao
- Funds for International Cooperation and Exchange between China-Sweden of the National Natural Science Foundation of China [81621064, 815290 03, 81370 089, 81361138020]
Introduction: The emergence of drug-resistant Gram-negative bacteria is a serious clinical problem that causes increased morbidity and mortality. However, the slow discovery of new antibiotics is unable to meet the need for treating bacterial infections caused by drug-resistant strains. Lipopolysaccharide (LPS) is synthesized in the cytoplasm and transported to the cell envelope by the LPS transport (Lpt) system. LptA and LptC form a complex that transports LPS from the inner membrane to the outer membrane. Methods: This study performed a screen for agents that disrupt the transport of LPS in Gram-negative bacteria Escherichia coli. It established a yeast two-hybrid system to detect LptA-LptC interaction and used this system to identify a compound, IMB-881, that blocks this interaction and shows antibacterial activity. Results: This study demonstrated that the IMB-881 compound specifically binds to LptA to disrupt LptA-LptC interaction using surface plasmon resonance assay. Overproduction of LptA protein but not that of LptC lowered the antibacterial activity of IMB-881. Strikingly, Escherichia coli cells accumulated 'extra' membrane material in the periplasm and exhibited filament morphology after treatment with IMB-881. Conclusion: This study successfully identified, by using a yeast two-hybrid system, an antibacterial agent that likely blocks LPS transport in Gram-negative bacteria. (C) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
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