Shahrour Hawraa, Alves Ferreira Daniela, Fitzgerald-Hughes Deirdre, O'Gara James P, Coffey Aidan, O'Neill Eoghan
Department of Clinical Microbiology, RCSI Education & Research Centre, Beaumont Hospital, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Department of Microbiology, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
Microbiol Spectr. 2025 Sep 2;13(9):e0071625. doi: 10.1128/spectrum.00716-25. Epub 2025 Aug 5.
The pathogenesis of acute and chronic wound infections is associated with biofilm formation. This study investigated the antimicrobial and antibiofilm potential of CHAPK-SH3blys, a bacteriophage-derived endolysin, against strains implicated in chronic wound infections. CHAPK-SH3blys exhibited potent antibacterial activity with a minimum inhibitory concentration (MIC) of 3.9 µg/mL. Biofilm assays conducted under static and dynamic wound-like conditions showed a concentration-dependent reduction in biofilm metabolic activity, with up to a 4-log reduction in viable cells at concentrations 50 times the MIC. Further investigations revealed that CHAPK-SH3blys showed biocompatibility with human cell lines and did not induce an inflammatory response. Notably, prolonged exposure to sub-MIC levels did not lead to resistance development in . These findings highlight CHAPK-SH3blys as a promising therapeutic agent for the treatment of biofilm-associated wound infections.IMPORTANCESuccessful treatment of wound infections, which is most commonly caused by the bacteria , is compromised by bacterial colonization resulting in slime layer or biofilm formation in the wound bed. Associated antimicrobial resistance (AMR) and limited treatment options can also impair wound healing and further highlight the need for the development and use of novel antimicrobial therapies. This study explores the antibiofilm and antimicrobial effectiveness of a bacteriophage-derived endolysin named CHAPK-SH3blys against strains implicated in chronic wound infections. Bacteriophage-derived endolysin represents novel antimicrobial agents, and in this study, we demonstrate the effectiveness of this agent in treating wound and biofilm- related infections under wound-like conditions in the laboratory without affecting the immune response or inducing antimicrobial resistance. Due to the urgent public health need to develop alternative antimicrobial agents to combat biofilm-associated infections, our study highlights CHAPK-SH3blys as a promising and exciting candidate for further therapeutic development.
急慢性伤口感染的发病机制与生物膜形成有关。本研究调查了噬菌体来源的内溶素CHAPK-SH3blys对与慢性伤口感染相关菌株的抗菌和抗生物膜潜力。CHAPK-SH3blys表现出强大的抗菌活性，最低抑菌浓度（MIC）为3.9μg/mL。在静态和动态伤口样条件下进行的生物膜试验表明，生物膜代谢活性呈浓度依赖性降低，在MIC的50倍浓度下，活细胞数量最多可减少4个对数级。进一步研究表明，CHAPK-SH3blys与人细胞系具有生物相容性，且不会引发炎症反应。值得注意的是，长时间暴露于亚MIC水平不会导致[具体细菌名称未给出]产生耐药性。这些发现突出了CHAPK-SH3blys作为治疗生物膜相关伤口感染的一种有前景的治疗剂。重要性伤口感染最常见由[具体细菌名称未给出]引起，其成功治疗因细菌定植导致伤口床形成黏液层或生物膜而受到影响。相关的抗菌耐药性（AMR）和有限的治疗选择也会损害伤口愈合，并进一步凸显了开发和使用新型抗菌疗法的必要性。本研究探讨了一种名为CHAPK-SH3blys的噬菌体来源内溶素对与慢性伤口感染相关菌株的抗生物膜和抗菌效果。噬菌体来源的内溶素代表新型抗菌剂，在本研究中，我们证明了该剂在实验室伤口样条件下治疗伤口和生物膜相关感染的有效性，且不影响免疫反应或诱导抗菌耐药性。由于迫切需要开发替代抗菌剂来对抗生物膜相关感染这一公共卫生需求，我们的研究突出了CHAPK-SH3blys作为进一步治疗开发的一个有前景且令人兴奋的候选物。
