Institute of Biotechnology and Biomedicine, Autonomous University of Barcelona, Barcelona, Spain.
Department of Genetics and Microbiology, Autonomous University of Barcelona, Barcelona, Spain.
Microb Biotechnol. 2024 Jun;17(6):e14483. doi: 10.1111/1751-7915.14483.
Antimicrobial resistance (AMR) is an escalating global health crisis, driven by the overuse and misuse of antibiotics. Multidrug-resistant Gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, are particularly concerning due to their high morbidity and mortality rates. In this context, endolysins, derived from bacteriophages, offer a promising alternative to traditional antibiotics. This study introduces LysJEP8, a novel endolysin derived from Escherichia phage JEP8, which exhibits remarkable antimicrobial activity against key Gram-negative members of the ESKAPE group. Comparative assessments highlight LysJEP8's superior performance in reducing bacterial survival rates compared to previously described endolysins, with the most significant impact observed against P. aeruginosa, and notable effects on A. baumannii and K. pneumoniae. The study found that LysJEP8, as predicted by in silico analysis, worked best at lower pH values but lost its effectiveness at salt concentrations close to physiological levels. Importantly, LysJEP8 exhibited remarkable efficacy in the disruption of P. aeruginosa biofilms. This research underscores the potential of LysJEP8 as a valuable candidate for the development of innovative antibacterial agents, particularly against Gram-negative pathogens, and highlights opportunities for further engineering and optimization to address AMR effectively.
抗微生物药物耐药性（AMR）是一场不断升级的全球卫生危机，其根源是抗生素的过度和不当使用。多药耐药革兰氏阴性菌，如铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌，由于其高发病率和死亡率，尤其令人担忧。在这种情况下，来源于噬菌体的内溶素为传统抗生素提供了一种有前途的替代方法。本研究介绍了 LysJEP8，这是一种来源于大肠杆菌噬菌体 JEP8 的新型内溶素，对 ESKAPE 组的关键革兰氏阴性成员具有显著的抗菌活性。比较评估突出了 LysJEP8 在降低细菌存活率方面优于先前描述的内溶素，对铜绿假单胞菌的影响最为显著，对鲍曼不动杆菌和肺炎克雷伯菌也有显著影响。研究发现，正如计算机分析预测的那样，LysJEP8 在较低的 pH 值下效果最佳，但在接近生理水平的盐浓度下失去了效力。重要的是，LysJEP8 对铜绿假单胞菌生物膜的破坏具有显著的疗效。这项研究强调了 LysJEP8 作为开发创新型抗菌剂的有价值候选物的潜力，特别是针对革兰氏阴性病原体，并且突出了进一步工程和优化以有效应对 AMR 的机会。
