Shahrour Hawraa, Ferreira Daniela Alves, Sheridan Luke, Fitzgerald-Hughes Deirdre, O'Gara James P, Devocelle Marc, Kelly Helena, O'Neill Eoghan
Department of Clinical Microbiology, RCSI Education and Research Centre, Beaumont Hospital, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Front Microbiol. 2025 Apr 24;16:1571649. doi: 10.3389/fmicb.2025.1571649. eCollection 2025.
Acute and chronic wound infections involving biofilms and caused by antimicrobial resistant (AMR) pathogens present significant challenges in healthcare, leading to substantial patient morbidity, increased hospital stays, and rising healthcare costs. Novel antimicrobial therapies are urgently needed to address these infections.
A screening of multiple antimicrobial peptides (AMPs) was performed and the most potent candidate, D-Bac8c, was tested against monospecies and polymicrobial biofilms of and using static and dynamic models. Cytotoxicity was evaluated on human cell lines, and the peptide was incorporated into a methylcellulose hydrogel to assess sustained release and antimicrobial efficacy as a hydrogel dressing.
D-Bac8c significantly reduced biofilm viability in both monospecies and polymicrobial biofilms. In static biofilm assays, treatment led to a 2-3 log reduction in bacterial load compared to untreated controls. In Duckworth biofilm flow device, a similar reduction was observed, demonstrating efficacy in conditions mimicking wound environments. Furthermore, D-Bac8c exhibited low cytotoxicity against human cell lines, and its incorporation into a methylcellulose hydrogel facilitated sustained release and enhanced antimicrobial activity. Furthermore, the peptide-loaded hydrogel showed considerable efficacy in disrupting pre-formed biofilms, underscoring its potential as a novel treatment for acute and chronic wound infections.
These findings highlight the potential of D-Bac8c to help address the urgent need for effective therapies against AMR pathogens and biofilm-associated wound infections. Further studies should focus on efficacy to optimize its therapeutic application in wound care.
由耐抗菌药物(AMR)病原体引起的涉及生物膜的急慢性伤口感染给医疗保健带来了重大挑战,导致患者出现严重发病情况、住院时间延长以及医疗成本上升。迫切需要新的抗菌疗法来应对这些感染。
对多种抗菌肽(AMPs)进行了筛选,并使用静态和动态模型对最有效的候选物D-Bac8c针对金黄色葡萄球菌和铜绿假单胞菌的单菌种和多菌种生物膜进行了测试。在人类细胞系上评估了细胞毒性,并将该肽掺入甲基纤维素水凝胶中,以评估其作为水凝胶敷料的缓释和抗菌效果。
D-Bac8c显著降低了单菌种和多菌种生物膜中的生物膜活力。在静态生物膜试验中,与未处理的对照相比,处理导致细菌载量降低2-3个对数。在达克沃思生物膜流动装置中也观察到了类似的降低,证明了其在模拟伤口环境条件下的有效性。此外,D-Bac8c对人类细胞系表现出低细胞毒性,将其掺入甲基纤维素水凝胶中有助于缓释并增强抗菌活性。此外,载有该肽的水凝胶在破坏预先形成的生物膜方面显示出相当大的效果,突出了其作为急慢性伤口感染新疗法的潜力。
这些发现突出了D-Bac8c在满足对抗AMR病原体和生物膜相关伤口感染的有效疗法的迫切需求方面的潜力。进一步的研究应侧重于其在伤口护理中的疗效,以优化其治疗应用。