Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 4, Pages 1430-1434Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201912137
Keywords
antibiotics; endotoxin; Gram-negative bacteria; gold nanosheets; supramolecular chemistry
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Funding
- NHRI [NHRI-BN-107-PP-30]
- Ministry of Science and Technology of Taiwan [MOST-106-2113-M-400-005-MY3]
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A strong interaction between colistin, a last-resort antibiotic of the polymyxin family, and free lipopolysaccharide (LPS, also referred to as endotoxin), released from the Gram-negative bacterial (GNB) outer membrane (OM), has been identified that can decrease the antibacterial efficacy of colistin, potentially increasing the dose of this antibiotic required for treatment. The competition between LPS in the GNB OM and free LPS for the interaction with colistin was prevented by using a supramolecular trap to capture free LPS. The supramolecular trap, fabricated from a subnanometer gold nanosheet with methyl motifs (SAuM), blocks lipid A, preventing the interaction between lipid A and colistin. This can minimize endotoxemia and maximize the antibacterial efficacy of colistin, enabling colistin to be used at lower doses. Thus, the potential crisis of colistin resistance could be avoided.
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