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Here, a novel heterogenization\u2010phase\u2010separated nano\u2010antibiotics (\n                    <jats:bold>NCefoTs<\/jats:bold>\n                    ) is proposed, through the co\u2010assembly of enzyme\u2010inhibiting lipopeptides (ELp component), membrane\u2010recognizing and disrupting lipopeptides (MLp component), and cefoperazone. The self\u2010sorting components of MLp\u00a0\u201cconcentrated island\u2010liked clusters\u201d\u00a0on the surface of\n                    <jats:bold>NCefoTs<\/jats:bold>\n                    promote the efficient penetration of\n                    <jats:bold>NCefoTs<\/jats:bold>\n                    through the outer membrane. Triggered by the DsbA, the precisely spatiotemporal engineered\n                    <jats:bold>NCefoTs<\/jats:bold>\n                    transform to nanofibers in\u00a0situ and further significantly enhance the inhibition of DsbA. The hydrolytic activity of \u03b2\u2010lactamase and the motility function of flagella are thereby impeded, confirming the efficacy of\n                    <jats:bold>NCefoTs<\/jats:bold>\n                    in restoring susceptibility to antibiotics and inhibiting infection dissemination. By these synergistic effects of\n                    <jats:bold>NCefoTs<\/jats:bold>\n                    , the minimum inhibitory concentration of antibiotics\u00a0decreases from over 300 \u00b5M to 1.56 \u00b5M for clinically isolated\n                    <jats:italic>E. coli<\/jats:italic>\n                    MDR. The survival rate of sepsis\u2010inflicted mice is significantly enhanced from 0% to 92% upon encapsulation of cefoperazone in\n                    <jats:bold>NCefoTs<\/jats:bold>\n                    , which rapidly eliminates invading pathogens and mitigates inflammation. The universally applicable delivery system, based on an \u201con demands\u201d strategy, presents a promising prospect for undruggable antibiotic targets in the periplasm to combat MDR bacteria.\n                  <\/jats:p>","DOI":"10.1002\/adma.202407152","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T04:17:32Z","timestamp":1726460252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Phase\u2010Separated Nano\u2010Antibiotics Enhanced Survival in Multidrug\u2010Resistant\n                    <i>Escherichia coli<\/i>\n                    Sepsis by Precise Periplasmic\n                    <i>Ec<\/i>\n                    DsbA Targeting"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3350-9949","authenticated-orcid":false,"given":"Pengfei","family":"Zou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Toxicology and 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100850 China"},{"name":"School of Pharmacy Henan University  Kaifeng Henan 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology  Beijing 100850 China"},{"name":"School of Chemical and Pharmaceutical Engineering Hebei University of Science and Technology  Shijiazhuang Hebei 050018 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Che","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology  Beijing 100850 China"},{"name":"School of Pharmaceutical Sciences &amp; Institute of Materia Medica Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Jinan Shandong 250117 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