Son Bokyung, Kong Minsuk, Lee Yoona, Ryu Sangryeol
Department of Food and Animal Biotechnology, Seoul National University, Seoul, South Korea.
Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
Front Microbiol. 2021 Jan 15;11:615887. doi: 10.3389/fmicb.2020.615887. eCollection 2020.
As the incidence of antibiotic-resistant bacteria has become increased, phage endolysins are believed as one of the promising alternatives to antibiotics. However, the discovery of potent endolysin is still challenging because it is labor intensive and difficult to obtain a soluble form with high lytic activity. In this respect, the modular structures of Gram-positive endolysins can provide an opportunity to develop novel endolysins by domain rearrangement. In this study, a random domain swapping library of four different endolysins from phages infecting was constructed and screened to obtain engineered endolysins. The novel chimeric endolysin, Lys109 was selected and characterized for its staphylolytic activity. Lys109 exhibited greater bacterial cell lytic activity than its parental endolysins against staphylococcal planktonic cells and biofilms, showing highly improved activity in eliminating from milk and on the surface of stainless steel. These results demonstrate that a novel chimeric endolysin with higher activity and solubility can be developed by random domain swapping and that this chimeric endolysin has a great potential as an antimicrobial agent.
随着抗生素耐药菌的发病率不断上升，噬菌体溶菌酶被认为是抗生素的一种有前途的替代品。然而，发现强效溶菌酶仍然具有挑战性，因为这一过程劳动强度大，且难以获得具有高裂解活性的可溶形式。在这方面，革兰氏阳性菌溶菌酶的模块化结构可为通过结构域重排开发新型溶菌酶提供机会。在本研究中，构建并筛选了来自感染[具体细菌名称缺失]的噬菌体的四种不同溶菌酶的随机结构域交换文库，以获得工程化溶菌酶。筛选出新型嵌合溶菌酶Lys109，并对其葡萄球菌溶解活性进行了表征。Lys109对葡萄球菌浮游细胞和生物膜的细菌细胞裂解活性高于其亲本溶菌酶，在从牛奶和不锈钢表面消除[具体细菌名称缺失]方面表现出显著提高的活性。这些结果表明，通过随机结构域交换可以开发出具有更高活性和溶解性的新型嵌合溶菌酶，并且这种嵌合溶菌酶作为抗菌剂具有巨大潜力。
