中文摘要：治疗多药耐药(MDR)革兰氏阴性菌引起的感染难度很大，使用噬菌体衍生的分解酶是一种潜在的解决方案。但由于革兰氏阴性细菌具有不透水的外膜，使噬菌体细胞溶解酶的外源性作用受阻。不过，最近研究表明，一些细胞溶解酶在信号肽的帮助下能够渗透革兰氏阴性菌外膜。本研究分析了309个侵感染革兰氏阴性病原体的噬菌体基因组，以确定含信号肽细胞溶解酶的进化标记。全基因组显示有265种推测的细胞溶解酶，其中17种含有信号捕获-释放基序，41种含有可裂解的信号肽。宿主特异性与细胞溶解酶多样性之间无明显关系。不过，一旦泛基因组聚类和细胞溶解酶多样性相关联，则细胞溶解酶基因的进化可能与噬菌体基因组其余部分相关。此外，信号肽和含信号捕获-释放的细胞溶解酶在蛋白分枝图中呈单系分布，提示不依赖于holin的细胞溶解酶的自然选择是有分歧的。本研究从265个潜在候选药物中筛选了58个用于体外抗MDR细菌实验。
外文摘要：Treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria is challenging, a potential solution for which is the use of bacteriophage-derived lytic enzymes. However, the exogenous action of bacteriophage lysins against Gram-negative bacteria is hindered due to the presence of an impermeable outer membrane in these bacteria. Nevertheless, recent research has demonstrated that some lysins are capable of permeating the outer membrane of Gram-negative bacteria with the help of signal peptides. In the present study, we investigated the genomes of 309 bacteriophages that infect Gram-negative pathogens of clinical interest in order to determine the evolutionary markers of signal peptide-containing lysins. Complete genomes displayed 265 putative lysins, of which 17 (6.41%) con-tained signal-arrest-release motifs and 41 (15.47%) contained cleavable signal peptides. There was no apparent relationship between host specificity and lysin diversity. Nevertheless, the evolution of lysin genes might not be independent of the rest of the bacteriophage genome once pan-genome clustering and lysin diversity appear to be correlated. In addition, signal peptide-and signal-arrest-release-containing lysins were monophyletically distributed in the protein cladogram, suggesting that the nat-ural selection of holin-independent lysins is divergent. Our study screened 58 (21.89%) out of 265 po-tential candidates for in vitro experimentation against MDR bacteria.
外文关键词：ESKAPE；Nosocomial pathogen；Bacteriophage-derived lytic enzyme； Enzybiotic；Antibiotic substitute
作者：Gontijo, MTP；Vidigal, PMP；Lopez, MES；Brocchi, M
作者单位：Univ Estadual Campinas UNICAMP；Univ Fed Vicosa UFV；Univ Cordoba
期刊名称：RESEARCH IN MICROBIOLOGY
期刊影响因子：3.217
出版年份：2021
出版刊次：2
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