中文摘要：耐多药革兰氏阴性菌的流行是一个公共卫生问题。有研究用噬菌体和噬菌体衍生的裂解酶来应对耐多药细菌的出现。在重组蛋白表达过程中，通过密码子优化和诱导pET型质粒低水平表达和控制培养条件，避免了tRNAs的可用性和内溶素毒性。使用多组氨酸标记促进了内溶素的纯化并改变了抗菌活性。外膜渗透剂，如有机酸，与内溶素协同作用，但一些内溶素本身可渗透革兰氏阴性菌的外膜。然而，内溶素的外膜渗透机制尚不清楚。其他策略，如内溶素与多粘菌素、银纳米颗粒和脂质体的联合给药可增加外膜渗透。包含外膜渗透结构域的工程化内溶素也可用于当前控制耐多药革兰氏阴性菌。宏基因组学是从未培养的噬菌体基因组中筛选具有抗菌特性的内溶素的一种新策略。本文回顾了内溶素异源表达的研究现状，展示了噬菌体内溶素在控制细菌感染方面的潜力。
外文摘要：The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization and lower expression levels using inducible pET-type plasmids and controlled cultivation conditions, respectively. The use of polyhistidine tags facilitates endolysin purification and alters antimicrobial activity. Outer membrane permeabilizers, such as organic acids, act synergistically with endolysins, but some endolysins permeate the outer membrane of Gram-negative bacteria per se. However, the outer membrane permeation mechanisms of endolysins remain unclear. Other strategies, such as the co-administration of endolysins with polymyxins, silver nanoparticles, and liposomes confer additional outer membrane permeation. Engineered endolysins comprising domains for outer membrane permeation is also a strategy used to overcome the current challenges on the control of multidrug-resistant Gram-negative bacteria. Metagenomics is a new strategy for screening endolysins with interesting antimicrobial properties from uncultured phage genomes. Here, we review the current state of the art on the heterologous expression of endolysin, showing the potential of bacteriophage endolysins in controlling bacterial infections.
外文关键词：nosocomial pathogen；bacteriophage；enzybiotic；peptide tag；bactericidal activity；biocontrol；antibiotic substitute
作者：Gontijo, MTP；Jorge, GP；Brocchi, M
作者单位：Univ Estadual Campinas
期刊名称：ANTIBIOTICS-BASEL
期刊影响因子：3.893
出版年份：2021
出版刊次：10
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