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The outer membrane integrity of most Gram\u2010negative bacteria critically depends on the lipopolysaccharide (LPS) transport (Lpt) system, which mediates LPS translocation from the inner to the outer membrane. In this study, we perform a structure\u2010based virtual screen against the Lpt system of\n                    <jats:italic>Acinetobacter<\/jats:italic>\n                    and identify a somatostatin octapeptide analogue (termed C4) as a candidate hit. Notably, C4 demonstrates modest antibacterial activity but exhibits robust synergistic activity with colistin. Integrated lipidomic and transcriptomic analyses reveal that C4 treatment induces membrane lipid remodeling, particularly a selective accumulation of phosphatidylglycerol (PG), which was associated with enhanced colistin activity. Moreover, C4 exposure significantly upregulates\n                    <jats:italic>mlaC<\/jats:italic>\n                    expression, a key determinant of phospholipid retrograde transport. Deletion of\n                    <jats:italic>mlaC<\/jats:italic>\n                    reduces C4\u2010induced PG enrichment and abolishes C4\u2010mediated potentiation of colistin, whereas\n                    <jats:italic>mlaC<\/jats:italic>\n                    overexpression enhances this potentiation and complementation partially restores it. In murine pneumonia and thigh infection models, the C4\u2010colistin combination significantly reduces bacterial burden and inflammatory cytokine levels, and attenuates histopathological damage. Our findings highlight the anti\u2010infective potential of targeting the Lpt system through membrane lipid remodeling and underscore C4 as a promising colistin adjuvant for combating\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1002\/advs.76198","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T08:50:11Z","timestamp":1781859011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Lipopolysaccharide Transport Induces Membrane Lipid Remodeling and Sensitizes\n                    <i>Acinetobacter baumannii<\/i>\n                    to Colistin Treatment"],"prefix":"10.1002","volume":"13","author":[{"given":"Jianya","family":"Luo","sequence":"first","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetianzi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinju","family":"Cai","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary Medicine 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