Department of Food and Animal Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
ACS Infect Dis. 2021 Aug 13;7(8):2081-2092. doi: 10.1021/acsinfecdis.0c00812. Epub 2021 May 28.
The increase in the prevalence of multidrug-resistant (MDR) with strong biofilm-forming capacity poses a serious public health concern. Endolysins derived from bacteriophages are a promising solution for antibiotic resistance problems. However, some natural staphylococcal endolysins have several shortcomings, such as low solubility and high sequence homology among domains. To overcome these limitations, we constructed a hybrid endolysin library by swapping an enzymatically active domain (EAD) and a cell wall binding domain (CBD) of 12 natural staphylococcal endolysins. We found a novel chimeric endolysin, ClyC, which showed enhanced lytic activity against compared to its parental endolysin forms. ClyC also exhibited strong antibacterial activity against in various biomatrices, such as milk and blood. Moreover, the treatment of chimeric endolysin effectively eradicated biofilms of multidrug-resistant bacteria, including methicillin-resistant (MRSA), (MRSE), and clinical isolates. In an in vivo mouse infection model, ClyC showed effective protection capability against methicillin-resistant (MRSA) without any toxic effects. Taken together, our data suggest that the chimeric endolysin ClyC can be considered a potential antibacterial agent against multidrug-resistant and may have clinical relevance.
具有强生物膜形成能力的多药耐药（MDR）的增加引起了严重的公共卫生关注。来自噬菌体的内溶素是解决抗生素耐药性问题的有前途的方法。然而，一些天然的葡萄球菌内溶素有几个缺点，例如低溶解度和结构域之间的高序列同源性。为了克服这些限制，我们通过交换 12 种天然葡萄球菌内溶素的酶活性结构域（EAD）和细胞壁结合结构域（CBD）构建了一个混合内溶素文库。我们发现了一种新型嵌合内溶素 ClyC，与亲本内溶素形式相比，其对 的裂解活性增强。ClyC 还表现出对牛奶和血液等各种生物基质中 的强大抗菌活性。此外，该嵌合内溶素的治疗有效地根除了包括耐甲氧西林金黄色葡萄球菌（MRSA）、耐甲氧西林表皮葡萄球菌（MRSE）和临床分离株在内的多药耐药菌的生物膜。在体内小鼠感染模型中，ClyC 对耐甲氧西林金黄色葡萄球菌（MRSA）表现出有效的保护能力，而没有任何毒副作用。总之，我们的数据表明，嵌合内溶素 ClyC 可以被认为是一种有潜力的抗多药耐药菌的抗菌剂，并且可能具有临床相关性。
