Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, United States.
ACS Nano. 2024 Oct 1;18(39):26928-26936. doi: 10.1021/acsnano.4c08671. Epub 2024 Sep 17.
The antibacterial efficacy and specificity of lytic bacteriophages (phages) make them promising therapeutics for treatment of multidrug-resistant bacterial infections. Restricted penetration of phages through the protective matrix of biofilms, however, may limit their efficacy against biofilm infections. Here, engineered polymers were used to generate noncovalent phage-polymer nanoassemblies (PPNs) that penetrate bacterial biofilms and kill resident bacteria. Phage K, active against multiple strains of , including methicillin-resistant (MRSA), was assembled with cationic poly(oxanorbornene) polymers into PPNs. The PPNs retained phage infectivity, while demonstrating enhanced biofilm penetration and killing relative to free phages. PPNs achieved 3-log bacterial reduction (∼99.9%) against MRSA biofilms PPNs were then incorporated into Poloxamer 407 (P407) hydrogels and applied onto wound biofilms, demonstrating controlled and sustained release. Hydrogel-incorporated PPNs were effective in a murine MRSA wound biofilm model, showing a 1.5-log reduction in bacterial load compared to a 0.5 log reduction with phage K in P407 hydrogel. Overall, this work showcases the therapeutic potential of phage K engineered with cationic polymers for treating wound biofilm infections.
溶菌噬菌体（噬菌体）的抗菌功效和特异性使它们成为治疗多药耐药细菌感染的有前途的治疗方法。然而，噬菌体通过生物膜的保护性基质的有限渗透可能会限制它们对生物膜感染的功效。在这里，工程聚合物被用于生成非共价噬菌体-聚合物纳米组装体（PPN），这些纳米组装体可以穿透细菌生物膜并杀死驻留细菌。针对包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的多种 菌株具有活性的噬菌体 K 与阳离子聚（降冰片烯）聚合物组装成 PPN。PPN 保留了噬菌体的感染力，同时相对于游离噬菌体显示出增强的生物膜穿透和杀菌能力。PPN 对 MRSA 生物膜实现了 3 对数的细菌减少（约 99.9%）。然后将 PPN 掺入泊洛沙姆 407（P407）水凝胶中，并应用于 伤口生物膜，表现出控制和持续释放。水凝胶中掺入的 PPN 在 MRSA 伤口生物膜模型中有效，与 P407 水凝胶中的噬菌体 K 相比，细菌负荷降低了 1.5 对数。总的来说，这项工作展示了用阳离子聚合物工程化的噬菌体 K 治疗伤口生物膜感染的治疗潜力。
