Authors
Lin Ruan, Cun Fan, Jingjie Chen, Yingxia Wang, Yuji Ren, Wenli Yuan, Xiaozhe Xiong, Chunming Guo
Published in
PloS one. Volume 21. Issue 7. Pages e0352997. Epub Jul 08, 2026.
Abstract
Recurrent urinary tract infections (UTIs) caused by multidrug-resistant uropathogenic Escherichia coli (UPEC) demand novel antimicrobial approaches. This study evaluated the membrane-intercalating conjugated oligoelectrolyte COE-D8 against 93 clinical UPEC isolates. While >75% of isolates exhibited high-level resistance to first-line antibiotics (MIC > 512 μg/mL), 94.6% remained susceptible to COE-D8 at ≤32 μg/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.
PMID:
42418411
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.
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