{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T18:47:23Z","timestamp":1783536443267,"version":"3.55.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460142"],"award-info":[{"award-number":["82460142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Yunnan Province of China","award":["202001BB050005"],"award-info":[{"award-number":["202001BB050005"]}]},{"name":"Xingdian talent support program of Yunnan Province"},{"name":"Guangdong Hybribio Biotech Funding","award":["H20230314, H20230311 and H20230313"],"award-info":[{"award-number":["H20230314, H20230311 and H20230313"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Recurrent urinary tract infections (UTIs) caused by multidrug-resistant uropathogenic\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (UPEC) demand novel antimicrobial approaches. This study evaluated the membrane-intercalating conjugated oligoelectrolyte COE-D8 against 93 clinical UPEC isolates. While &gt;75% of isolates exhibited high-level resistance to first-line antibiotics (MIC\u2009&gt;\u2009512 \u03bcg\/mL), 94.6% remained susceptible to COE-D8 at \u226432 \u03bcg\/mL. COE-D8 eliminated bacteria fourfold faster than standard antibiotics through membrane disruption driven by a dimensional mismatch with the lipid bilayer. To mitigate the inherent cytotoxicity of COE-D8 alone, we developed a synergistic co-administration strategy with fosfomycin. This approach achieved a significant dose-sparing effect, rescuing 7-day murine survival from 40% to 80% in safety models without compromising efficacy. Furthermore, resistance induction studies identified a high barrier to adaptation, with survival primarily mediated by mzrA mutations. These findings establish the COE-D8\/fosfomycin combination as a host-friendly, mechanism-driven strategy against refractory UPEC.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352997","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:32:16Z","timestamp":1783531936000},"page":"e0352997","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel COE-D8-fosfomycin conjugate effectively combats first-line antibiotic-resistant uropathogenic Escherichia coli"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7980-232X","authenticated-orcid":true,"given":"Lin","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cun","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhe","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6141-0037","authenticated-orcid":true,"given":"Chunming","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"issue":"1","key":"pone.0352997.ref001","first-page":"40","article-title":"Urinary tract infection in women","volume":"20","author":"K Czajkowski","year":"2021","journal-title":"Prz Menopauzalny"},{"issue":"2","key":"pone.0352997.ref002","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1067\/mda.2003.7","article-title":"Epidemiology of urinary tract infections: incidence, morbidity, and economic costs","volume":"49","author":"B Foxman","year":"2003","journal-title":"Dis Mon"},{"issue":"12","key":"pone.0352997.ref003","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrurol.2010.190","article-title":"The epidemiology of urinary tract infection","volume":"7","author":"B Foxman","year":"2010","journal-title":"Nat Rev Urol"},{"issue":"42","key":"pone.0352997.ref004","doi-asserted-by":"crossref","first-page":"16518","DOI":"10.1074\/jbc.RA118.003499","article-title":"Uropathogenic Escherichia coli invades bladder epithelial cells by activating kinase networks in host cells","volume":"293","author":"W-J Kim","year":"2018","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0352997.ref005","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/nrmicro2265","article-title":"Molecular mechanisms of Escherichia coli pathogenicity","volume":"8","author":"MA Croxen","year":"2010","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"pone.0352997.ref006","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrmicro1821","article-title":"Exit strategies of intracellular pathogens","volume":"6","author":"K Hybiske","year":"2008","journal-title":"Nat Rev Microbiol"},{"issue":"10","key":"pone.0352997.ref007","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/nrurol.2015.199","article-title":"The emerging threat of multidrug-resistant Gram-negative bacteria in urology","volume":"12","author":"HM Zowawi","year":"2015","journal-title":"Nat Rev Urol"},{"issue":"10","key":"pone.0352997.ref008","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3390\/pathogens10101310","article-title":"Bacterial Antibiotic Resistance: The Most Critical Pathogens","volume":"10","author":"G Mancuso","year":"2021","journal-title":"Pathogens"},{"issue":"12","key":"pone.0352997.ref009","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1128\/AAC.44.12.3317-3321.2000","article-title":"Interactions of bacterial cationic peptide antibiotics with outer and cytoplasmic membranes of Pseudomonas aeruginosa","volume":"44","author":"L Zhang","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0352997.ref010","first-page":"21","volume-title":"Pili and Flagella. 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