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Few drugs have been proven to kill bacteria and simultaneously neutralize LPS toxicity. Here, the chimeric peptides-R7, A7 and G7 were generated by connecting LBP14 (LPS-targeting domain) with L7 (killing domain) via different linkers to improve antibacterial and anti-inflammatory activities. Compared to parent LBP14-RKRR and L7, the antibacterial activity of R7 with a cleavable \u201cRKRR\u201d linker and the \u201cLBP14-RKRR\u2009+\u2009L7\u201d cocktail against <jats:italic>Escherichia coli<\/jats:italic>, <jats:italic>Salmonella typhimurium<\/jats:italic> and <jats:italic>Staphylococcus aureus<\/jats:italic> was increased by 2\u2009~\u20094-fold. Both A7 and G7 with non-cleavable linkers almost lost antibacterial activity. The ability of R7 to neutralize LPS was markedly higher than that of LBP14-RKRR and L7. In vivo, R7 could be cleaved by furin in a time-dependent manner, and release L7 and LBP14-RKRR in serum. In vivo, R7 can enhance mouse survival more effectively than L7 and alleviate lung injuries by selective inhibition of the NF-\u03baB signaling pathways and promoting higher IAP activity. It suggests that R7 may be promising dual-function candidates as antibacterial and anti-endotoxin agents.<\/jats:p>","DOI":"10.1038\/s42003-023-05528-0","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T15:02:56Z","timestamp":1700146976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A cleavable chimeric peptide with targeting and killing domains enhances LPS neutralization and antibacterial properties against multi-drug resistant E. coli"],"prefix":"10.1038","volume":"6","author":[{"given":"Zhenlong","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8179-074X","authenticated-orcid":false,"given":"Xiumin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4048-6055","authenticated-orcid":false,"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,16]]},"reference":[{"key":"5528_CR1","doi-asserted-by":"publisher","first-page":"e0130105","DOI":"10.1371\/journal.pone.0130105","volume":"10","author":"F Chowdhury","year":"2015","unstructured":"Chowdhury, F. et al. 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