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结构特征、作用机制及 II 类细菌素实际应用前景。

Structural Features, Mechanisms of Action, and Prospects for Practical Application of Class II Bacteriocins.

机构信息

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.

出版信息

Biochemistry (Mosc). 2022 Nov;87(11):1387-1403. doi: 10.1134/S0006297922110165.

DOI:10.1134/S0006297922110165
PMID:36509729
Abstract

Bacteriocins are antimicrobial peptides ribosomally synthesized by both Gram-negative and Gram-positive bacteria, as well as by archaea. Bacteriocins are usually active against phylogenetically related bacteria, providing competitive advantage to their producers in the natural bacterial environment. However, some bacteriocins are known to have a broader spectrum of antibacterial activity, including activity against multidrug-resistant bacterial strains. Multitude of bacteriocins studied to date are characterized by a wide variety of chemical structures and mechanisms of action. Existing classification systems for bacteriocins take into account structural features and biosynthetic pathways of bacteriocins, as well as the phylogenetic affiliation of their producing organisms. Heat-stable bacteriocins with molecular weight of less than 10 kDa from Gram-positive and Gram-negative producers are divided into post-translationally modified (class I) and unmodified peptides (class II). In recent years there has been an increasing interest in the class II bacteriocins as potential therapeutic agents that can help to combat antibiotic-resistant infections. Advantages of unmodified peptides are relative simplicity of their biotechnological production in heterologous systems and chemical synthesis. Potential for the combined use of bacteriocins with other antimicrobial agents allowing to enhance their efficacy, low probability of cross-resistance development, and ability of probiotic strains to produce bacteriocins in situ make them promising candidate compounds for creation of new drugs. The review focuses on structural diversity of the class II bacteriocins and their practical relevance.

摘要

细菌素是由革兰氏阴性和革兰氏阳性细菌以及古菌通过核糖体合成的抗菌肽。细菌素通常对系统发育上相关的细菌具有活性,为其生产者在自然细菌环境中提供竞争优势。然而,一些细菌素有更广谱的抗菌活性,包括对抗多药耐药菌的活性。迄今为止,大量研究的细菌素有多种化学结构和作用机制。现有的细菌素分类系统考虑了细菌素的结构特征和生物合成途径,以及其产生菌的系统发育关系。来自革兰氏阳性和革兰氏阴性生产者的热稳定、分子量小于 10 kDa 的细菌素分为翻译后修饰(I 类)和未修饰肽(II 类)。近年来,人们对 II 类细菌素作为潜在治疗剂越来越感兴趣,因为它们可以帮助对抗抗生素耐药性感染。未修饰肽的优点是在异源系统和化学合成中相对简单的生物技术生产。细菌素与其他抗菌剂联合使用的潜力可以提高它们的疗效、降低交叉耐药性发展的可能性、以及益生菌株原位产生细菌素的能力,使它们成为创造新药的有前途的候选化合物。本综述重点介绍了 II 类细菌素的结构多样性及其实际意义。

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