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在临床环境中使用内切溶素的优势和挑战。

The Advantages and Challenges of Using Endolysins in a Clinical Setting.

机构信息

School of Microbiology, University College Cork, T12 YT20 Cork, Ireland.

APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland.

出版信息

Viruses. 2021 Apr 15;13(4):680. doi: 10.3390/v13040680.

Abstract

Antibiotic-resistant pathogens are increasingly more prevalent and problematic. Traditional antibiotics are no longer a viable option for dealing with these multidrug-resistant microbes and so new approaches are needed. Bacteriophage-derived proteins such as endolysins could offer one effective solution. Endolysins are bacteriophage-encoded peptidoglycan hydrolases that act to lyse bacterial cells by targeting their cell's wall, particularly in Gram-positive bacteria due to their naturally exposed peptidoglycan layer. These lytic enzymes have received much interest from the scientific community in recent years for their specificity, mode of action, potential for engineering, and lack of resistance mechanisms. Over the past decade, a renewed interest in endolysin therapy has led to a number of successful applications. Recombinant endolysins have been shown to be effective against prominent pathogens such as MRSA, strains in biofilm formation, and . Endolysins have also been studied in combination with other antimicrobials, giving a synergistic effect. Although endolysin therapy comes with some regulatory and logistical hurdles, the future looks promising, with the emergence of engineered "next-generation" lysins. This review will focus on the likelihood that endolysins will become a viable new antimicrobial therapy and the challenges that may have to be overcome along the way.

摘要

耐药病原体越来越普遍和棘手。传统抗生素不再是应对这些多药耐药微生物的可行选择,因此需要新的方法。噬菌体衍生的蛋白质,如溶菌酶,可以提供一种有效的解决方案。溶菌酶是噬菌体编码的肽聚糖水解酶,通过靶向细菌细胞壁发挥裂解细菌细胞的作用,特别是在革兰氏阳性菌中,因为它们的天然暴露的肽聚糖层。近年来,这些裂解酶因其特异性、作用模式、工程潜力和缺乏耐药机制而受到科学界的广泛关注。在过去的十年中,人们对溶菌酶治疗的重新关注导致了许多成功的应用。重组溶菌酶已被证明对包括耐甲氧西林金黄色葡萄球菌(MRSA)在内的主要病原体、生物膜形成菌株和 具有疗效。溶菌酶也与其他抗菌药物联合研究,产生协同作用。尽管溶菌酶治疗存在一些监管和后勤方面的障碍,但随着工程化的“下一代”溶菌酶的出现,前景看好。这篇综述将重点讨论溶菌酶是否有可能成为一种可行的新抗菌治疗方法,以及在这一过程中可能需要克服的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88b8/8071259/3ad715f4f906/viruses-13-00680-g001.jpg

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