中文摘要：噬菌体（内溶素）细胞裂解酶是对抗耐药细菌感染的常规抗生素化疗的可行替代品。细胞裂解酶的功能关系着其应用重点，然而，目前缺乏对与此相关的结构和性质的全面了解。已有研究表明，侵染革兰氏阴性菌（G-）的噬菌体细胞裂解酶的典型特征（较高的净电荷和两亲螺旋）是改善与G-包膜相互作用的原因。这些类抗菌肽（AMP）元件在抗菌分子设计中也具有重要意义。因此，本研究旨在提供噬菌体细胞裂解酶的主要结构的最新观点，以阐明几个序列预测性质的进化重要性，特别是与G表面的相互作用；构建了包含2182条细胞裂解酶序列的数据库，其中包含相关信息，如结构域结构、噬菌体宿主细菌的数据和序列预测的理化特性。基于此，对某些特征的差异表现进行了调查；揭示了不同的细胞裂解酶结构变体，这些变体大多在侵染某些细菌宿主的噬菌体中发现。特别地，一些理化性质（较高的净电荷、疏水性、疏水力矩和脂肪族指数）与G-噬菌体细胞裂解酶有关，特异出现在其C-末端；提供了有关细菌宿主特征的细胞裂解酶显著遗传专一性信息，特别支持目前的普遍性假设，即来自G-的细胞裂解酶通常包含AMP样区域。
    重点：噬菌体编码的裂解酶，也称为细胞裂解酶，是常用抗生素最有希望的替代品之一。细胞裂解酶作为新型抗菌剂对付抗生素耐药菌的潜力不仅来源于其引发耐药性的机会较低等特点，还来源于其作为合成生物学部分的多功能性。由细胞裂解酶衍生的功能模块目前正用于设计具有所需特性的新型抗菌剂。本研究通过检测一组噬菌体细胞裂解酶基因，提供了细胞裂解酶多样性的观点。研究发现了以不同结构，从而决定侵染细菌细胞壁结构特化范围的噬菌体细胞裂解酶之间的根本差异。这些结果为支持当前文献中的一些常见假设提供了证据，并为进一步开发提供了更新和特征化的细胞裂解酶序列数据库。
外文摘要：Phage (endo)lysins are thought to be a viable alternative to usual antibiotic chemotherapy to fight resistant bacterial infections. However, a comprehensive view of lysins' structure and properties regarding their function, with an applied focus, is somewhat lacking. Current literature suggests that specific features typical of lysins from phages infecting Gram-negative bacteria (G-) (higher net charge and amphipathic helices) are responsible for improved interaction with the G- envelope. Such antimicrobial peptide (AMP)-like elements are also of interest for antimicrobial molecule design. Thus, this study aims to provide an updated view on the primary structural landscape of phage lysins to clarify the evolutionary importance of several sequence-predicted properties, particularly for the interaction with the G- surface. A database of 2,182 lysin sequences was compiled, containing relevant information such as domain architectures, data on the phages' host bacteria, and sequence-predicted physicochemical properties. Based on such classifiers, an investigation of the differential appearance of certain features was conducted. This analysis revealed different lysin architectural variants that are preferably found in phages infecting certain bacterial hosts. In particular, some physicochemical properties (higher net charge, hydrophobicity, hydrophobic moment, and aliphatic index) were associated with G-phage lysins, appearing specifically at their C-terminal end. Information on the remarkable genetic specialization of lysins regarding the features of the bacterial hosts is provided, specifically supporting the nowadays common hypothesis that lysins from G- usually contain AMP-like regions.
   IMPORTANCE Phage-encoded lytic enzymes, also called lysins, are one of the most promising alternatives to common antibiotics. The potential of lysins as novel antimicrobials to tackle antibiotic-resistant bacteria not only arises from features such as a lower chance to provoke resistance but also from their versatility as synthetic biology parts. Functional modules derived from lysins are currently being used for the design of novel antimicrobials with desired properties. This study provides a view of the lysin diversity landscape by examining a set of phage lysin genes. We have uncovered the fundamental differences between the lysins from phages that infect bacteria with different superficial architectures and, thus, the reach of their specialization regarding cell wall structures. These results provide clarity and evidence to sustain some of the common hypotheses in current literature, as well as making available an updated and characterized database of lysins sequences for further developments.
外文关键词：endolysins；bacteriophages；bacteriophage therapy；genomics；bioinformatics；antimicrobial agents
作者：Vazquez, R；Garcia, E；Garcia, P
作者单位：Ctr Invest Biol Margarita Salas；Ctr Invest Biomed Red Enfermedades Resp
期刊名称：JOURNAL OF VIROLOGY
期刊影响因子：4.501
出版年份：2021
出版刊次：14
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