中文摘要：面对多药耐药性(AMR)日益增长的威胁，人类努力从所有可能的地方，偏远地区土壤到深海，寻找抗生素候选药物和抗菌替代品。在这场“抗菌药物淘金热”中，研究人员转向细菌细胞的天敌--噬菌体，并发现它们是AMR细菌的丰富武器库。已经证明内溶素(细胞裂解酶)，一种噬菌体用来从内部破坏细菌细胞的酶，具有高度选择性和高效性，可以从外部杀死目标细菌，并保持较低的细菌耐药性。本文首先介绍了溶血素对革兰氏阳性(GM+)细菌的结构和作用机制，并概述了溶酶蛋白的发展历史。其次，详细介绍了它们对GM+细菌的安全性和有效性的最新临床前及临床研究，重点介绍了这些酶的配方策略。最后，讨论了存在的挑战和潜在障碍。尽管存在这些限制，但发展趋势表明，第一批经批准的细胞裂解酶药物即将面市。综上所述，本文及时总结了细胞裂解酶作为AMR GM+细菌抗菌酶的最新进展，为致力于对抗细菌感染的生物材料研究人员提供了指南。
外文摘要：Facing the increasing threat of multi-drug antimicrobial resistance (AMR), humans strive to search for antibiotic drug candidates and antibacterial alternatives from all possible places, from soils in remote areas to deep in the sea. In this "gold rush for antibacterials," researchers turn to the natural enemy of bacterial cells, bacteriophage (phages), and find them a rich source of weapons for AMR bacteria. Endolysins (lysins), the enzymes phages use to break the bacterial cells from within, have been shown to be highly selective and efficient in killing their target bacteria from outside while maintaining a low occurrence of bacterial resistance. In this review, we start with the structures and mechanisms of action of lysins against Gram-positive (GM+) bacteria. The developmental history of lysins is also outlined. Then, we detail the latest preclinical and clinical research on their safety and efficacy against GM+ bacteria, focusing on the formulation strategies of these enzymes. Finally, the challenges and potential hurdles are discussed. Notwithstanding these limitations, the trends in development indicate that the first, approved lysin drugs will be available soon in the near future. Overall, this review presents a timely summary of the current progress on lysins as antibacterial enzymes for AMR GM+ bacteria, and provides a guidebook for biomaterial researchers who are dedicating themselves to the battle against bacterial infections.
外文关键词：Lysins；multidrug-resistant；antibiotic-resistant；bacterial infections；gram-positive bacteria；formulation and delivery
作者：Ho, MKY；Zhang, PF；Chen, X；Xia, J；Leung, SSY
作者单位：Chinese Univ Hong Kong
期刊名称：CRITICAL REVIEWS IN MICROBIOLOGY
期刊影响因子：7.349
出版年份：2021
出版刊次：
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