São-José Carlos
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Antibiotics (Basel). 2018 Mar 22;7(2):29. doi: 10.3390/antibiotics7020029.
Lytic enzymes encoded by bacteriophages have been intensively explored as alternative agents for combating bacterial pathogens in different contexts. The antibacterial character of these enzymes (enzybiotics) results from their degrading activity towards peptidoglycan, an essential component of the bacterial cell wall. In fact, phage lytic products have the capacity to kill target bacteria when added exogenously in the form of recombinant proteins. However, there is also growing recognition that the natural bactericidal activity of these agents can, and sometimes needs to be, substantially improved through manipulation of their functional domains or by equipping them with new functions. In addition, often, native lytic proteins exhibit features that restrict their applicability as effective antibacterials, such as poor solubility or reduced stability. Here, I present an overview of the engineering approaches that can be followed not only to overcome these and other restrictions, but also to generate completely new antibacterial agents with significantly enhanced characteristics. As conventional antibiotics are running short, the remarkable progress in this field opens up the possibility of tailoring efficient enzybiotics to tackle the most menacing bacterial infections.
噬菌体编码的裂解酶已被深入研究，作为在不同情况下对抗细菌病原体的替代剂。这些酶（酶抗生素）的抗菌特性源于它们对肽聚糖（细菌细胞壁的重要组成部分）的降解活性。事实上，当以重组蛋白的形式外源添加时，噬菌体裂解产物有能力杀死靶细菌。然而，人们也越来越认识到，通过操纵这些药物的功能域或赋予它们新功能，可以而且有时需要大幅提高这些药物的天然杀菌活性。此外，天然裂解蛋白通常表现出一些限制其作为有效抗菌剂适用性的特性，如溶解性差或稳定性降低。在这里，我概述了一些工程方法，这些方法不仅可以克服这些和其他限制，还可以生成具有显著增强特性的全新抗菌剂。由于传统抗生素日益短缺，该领域的显著进展为定制高效的酶抗生素以应对最具威胁性的细菌感染开辟了可能性。
