PDF(Pubmed)
Abstract：
Bacteriophage-encoded endolysins, peptidoglycan hydrolases breaking down the Gram-positive bacterial cell wall, represent a groundbreaking class of novel antimicrobials to revolutionize the veterinary medicine field. Wild-type endolysins exhibit a modular structure, consisting of enzymatically active and cell wall-binding domains, that enable genetic engineering strategies for the creation of chimeric fusion proteins or so-called \'engineered endolysins\'. This biotechnological approach has yielded variants with modified lytic spectrums, introducing new possibilities in antimicrobial development. However, the discovery of highly similar endolysins by different groups has occasionally resulted in the assignment of different names that complicate a straightforward comparison. The aim of this review was to perform a homology-based comparison of the wild-type and engineered endolysins that have been characterized in the context of bovine mastitis-causing streptococci and staphylococci, grouping homologous endolysins with ≥ 95.0% protein sequence similarity. Literature is explored by homologous groups for the wild-type endolysins, followed by a chronological examination of engineered endolysins according to their year of publication. This review concludes that the wild-type endolysins encountered persistent challenges in raw milk and in vivo settings, causing a notable shift in the field towards the engineering of endolysins. Lead candidates that display robust lytic activity are nowadays selected from screening assays that are performed under these challenging conditions, often utilizing advanced high-throughput protein engineering methods. Overall, these recent advancements suggest that endolysins will integrate into the antibiotic arsenal over the next decade, thereby innovating antimicrobial treatment against bovine mastitis-causing streptococci and staphylococci.
摘要：
噬菌体编码的内溶素，肽聚糖水解酶分解革兰氏阳性细菌细胞壁，代表了一类开创性的新型抗菌药物，彻底改变了兽医学领域。野生型内溶素表现出模块化结构，由酶活性和细胞壁结合结构域组成，这使得基因工程策略能够产生嵌合融合蛋白或所谓的“工程内溶素”。这种生物技术方法已经产生了具有修改的裂解光谱的变体，在抗微生物剂开发中引入新的可能性。然而,不同组发现高度相似的内溶素,有时会导致不同名称的分配,从而使直接比较复杂化.这篇综述的目的是对野生型和工程内溶素进行基于同源性的比较，这些内溶素在引起牛乳腺炎的链球菌和葡萄球菌的背景下进行了表征，将蛋白质序列相似性≥95.0％的同源内溶素分组。通过野生型内溶素的同源组探索文献，然后根据其出版年份对工程内溶素进行时间顺序检查。这篇综述得出结论，野生型内溶素在生乳和体内环境中遇到了持续的挑战，导致该领域向内溶素工程的显著转变。现在，从在这些具有挑战性的条件下进行的筛选测定中选择显示出强大裂解活性的前导候选物。经常利用先进的高通量蛋白质工程方法。总的来说,这些最近的进展表明，内溶素将在未来十年内整合到抗生素库中，从而创新抗微生物治疗牛乳腺炎引起的链球菌和葡萄球菌。
