Thienoacene-Based Conjugated Oligoelectrolytes for Membrane-Targeting Antimicrobial Approaches: Synergistic Biofilm Eradication and Antimicrobial Resistance Reversal

作者：Lin Chen, Lingna Wang, Yufei Mao, Hongsheng Hu, Lina Xu, Wei Shen, Bing Wang, Jian Xiao, Hailin Zhang, Chenyao Nie · 发表于：ACS Applied Materials & Interfaces · 年份：2025 · DOI：10.1021/acsami.5c05491 · 被引用次数：6 · 研究领域：Antimicrobial Peptides and Activities、Antimicrobial agents and applications、Polydiacetylene-based materials and applications

Membrane-targeting antimicrobials represent a promising class of materials to combat the escalating issue of antimicrobial resistance. Herein, we report a series of membrane-targeting conjugated oligoelectrolytes (COE- n T) featuring thienoacene moieties as π-conjugated cores, designed for tackling antimicrobial resistance. COE- n T exhibited higher activity against Gram-positive bacteria compared to Gram-negative bacteria, with no intrinsic resistance observed in either drug-resistant strain. Notably, a reduction in the π-conjugated length of COE- n T correlated with an increase in membrane permeability and toxicity toward cells and animals. Moreover, COE- n T demonstrated synergistic effects with commercial antibiotics against drug-resistant strains and restored susceptibility to ribosome-targeting antibiotics, such as clindamycin and erythromycin. To illustrate their synergistic potential, the combination of COE-4T and mupirocin was employed to treat methicillin-resistant Staphylococcus aureus infections in a murine wound model, resulting in significant biofilm eradication and enhanced antimicrobial efficacy. This new series of thienoacene-based COEs expands the antimicrobial COEs library with defined structure–activity relationship profiles and demonstrates its potential as a powerful adjunctive therapy for overcoming antimicrobial resistance.