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Bacteriophages that infect Gram-negative bacteria as source of signal-arrest-release motif lysins
Research in Microbiology ( IF 2.6 ) Pub Date : 2020-12-19 , DOI: 10.1016/j.resmic.2020.103794
Marco Túlio Pardini Gontijo 1 , Pedro Marcus Pereira Vidigal 2 , Maryoris Elisa Soto Lopez 3 , Marcelo Brocchi 1
Affiliation  

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%) contained 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 natural selection of holin-independent lysins is divergent. Our study screened 58 (21.89%) out of 265 potential candidates for in vitro experimentation against MDR bacteria.



中文翻译:

感染革兰氏阴性菌的噬菌体作为信号抑制释放基序溶素的来源

治疗由多重耐药 (MDR) 革兰氏阴性菌引起的感染具有挑战性,使用噬菌体衍生的裂解酶是一种潜在的解决方案。然而,由于不透水的存在,噬菌体溶素对革兰氏阴性菌的外源作用受到阻碍。这些细菌的外膜。然而,最近的研究表明,一些溶素能够在信号肽的帮助下渗透革兰氏阴性菌的外膜。在本研究中,我们研究了 309 种感染具有临床意义的革兰氏阴性病原体的噬菌体的基因组,以确定含有信号肽的溶素的进化标记。完整的基因组显示了 265 种推定的溶素,其中 17 种(6.41%)含有信号阻滞释放基序,41 种(15.47%)含有可切割的信号肽。宿主特异性和溶素多样性之间没有明显的关系。然而,一旦泛基因组聚类和溶素多样性似乎相关,溶素基因的进化可能不独立于噬菌体基因组的其余部分。此外,含有信号肽和信号阻滞释放的溶素在蛋白质分支图中单系分布,表明独立于穴蛋白的溶素的自然选择是不同的。我们的研究从 265 名潜在候选人中筛选了 58 名 (21.89%)针对 MDR 细菌的体外实验。

更新日期:2020-12-19
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