Liu Weilin, Zhang Jiang, Chen Liang
College of Bioengineering, Beijing Polytechnic University, Beijing 100176, China.
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Microorganisms. 2025 Aug 27;13(9):2002. doi: 10.3390/microorganisms13092002.
Persistent bacteria (PB) are a subpopulation of dormant cells that tolerate high antibiotic concentrations and cause chronic, hard-to-treat infections, posing a serious global health threat. In this study, the antibacterial efficacy of six cationic polymers, poly(hexamethylene guanidine) (PHMG), polyethyleneimines of different molecular weights, α-polylysine, ε-polylysine, and polyacrylamide, against persistent bacteria was systematically evaluated. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of these cationic polymers against susceptible and persistent methicillin-susceptible (MSSA), methicillin-resistant (MRSA), and () were determined using a microbroth dilution method, while cytotoxicity to mouse fibroblast (L929) cells was assessed via MTT assay. PHMG demonstrated superior antibacterial activity, with MBC values as low as 2 μg/mL against persistent MSSA, markedly outperforming the other polymers tested. The key novelties of this work are (i) the first establishment of a cationic polymer library with diverse structural parameters for persistent bacteria clearance, offering a potential strategy for treating recalcitrant infections; and (ii) the elucidation of quantitative correlations between polymer charge density and hydrophobic chain segments with antimicrobial efficacy through structure-activity relationship analysis, providing a theoretical basis for the rational design of anti-persistent materials.
持续菌（PB）是休眠细胞的一个亚群，能够耐受高浓度抗生素并导致慢性、难以治疗的感染，对全球健康构成严重威胁。在本研究中，系统评估了六种阳离子聚合物，即聚六亚甲基胍（PHMG）、不同分子量的聚乙烯亚胺、α-聚赖氨酸、ε-聚赖氨酸和聚丙烯酰胺对持续菌的抗菌效果。使用微量肉汤稀释法测定这些阳离子聚合物对敏感和持续的甲氧西林敏感（MSSA）、耐甲氧西林（MRSA）以及（此处原文括号内容缺失信息）的最低抑菌浓度（MIC）和最低杀菌浓度（MBC），同时通过MTT法评估对小鼠成纤维细胞（L929）的细胞毒性。PHMG表现出卓越的抗菌活性，对持续的MSSA的MBC值低至2μg/mL，明显优于其他测试聚合物。这项工作的关键创新点在于：（i）首次建立了具有不同结构参数的用于清除持续菌的阳离子聚合物库，为治疗顽固性感染提供了一种潜在策略；（ii）通过构效关系分析阐明了聚合物电荷密度和疏水链段与抗菌效果之间的定量相关性，为抗持续菌材料的合理设计提供了理论依据。
