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  • Title: Identification of an anti-Gram-negative bacteria agent disrupting the interaction between lipopolysaccharide transporters LptA and LptC.
    Author: Zhang X, Li Y, Wang W, Zhang J, Lin Y, Hong B, You X, Song D, Wang Y, Jiang J, Si S.
    Journal: Int J Antimicrob Agents; 2019 Apr; 53(4):442-448. PubMed ID: 30476569.
    Abstract:
    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.
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