Evidence for Widespread Class II Microcins in Enterobacterales Genomes.

Evidence for Widespread Class II Microcins in Enterobacterales Genomes.
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DOI:
10.1128/aem.01486-22
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发表时间:
2022-12-13
影响因子:
4.4
通讯作者:
--
中科院分区:
生物学2区
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微球菌素是由某些革兰氏阴性细菌产生的一类抗菌肽,用于杀死或抑制竞争细菌的生长。只有10种独特的、经过实验验证的II类微球蛋白被鉴定出来,其中大部分来自大肠杆菌。虽然目前微胶蛋白的代表性很少,但它们表现出一系列不同的分子功能、摄取机制和靶标特异性。从如此小的代表性中获得的这种广泛的多样性表明,微囊素可能具有从基因组数据集中进行生物勘探多肽抗生素的未开发潜力。我们使用一种系统的生物信息学方法在大肠杆菌及其科内的其他物种中寻找经过验证的和新的II类微球蛋白。近四分之一的大肠杆菌基因组组合含有一种或多种微菌素,其中对特定微菌素的命中率因分离的种子组而异。来自人类肠外和家禽肉类来源的大肠杆菌分离株的微球蛋白含量较高,而来自淡水的分离株则被耗尽。在肠杆菌科所有五个不同的系统发育谱系中都发现了不同丰度的微球菌素,其中在“克雷伯氏菌”分支中的流行率特别高。来自肠杆菌目物种的代表性基因组组件,以及少数外群物种,也包含推测的微型素序列。这项研究表明,微信蛋白有着复杂的进化史,远远超出了我们对目前已证实的微信蛋白的有限了解。对这些新发现的微球蛋白进行功能表征的努力,将极有可能开辟多肽抗生素和微生物组调节剂的新领域,并阐明细菌相互竞争的方式。重要性II类微菌素是由肠杆菌科中的革兰氏阴性菌菌株产生的小分子细菌素。人们普遍认为它们在细菌间的竞争中发挥了作用,尽管这方面的直接证据有限,而且它们可能在开发新的多肽抗生素方面提供信息。然而,已证实的II类微信的例子很少,而且由于其序列多样性,新的微信很难被识别,这使得将它们作为一个群体进行研究变得复杂。在这里,我们通过开发一种生物信息学管道来检测硅胶中的微球蛋白,从而克服了这一限制。利用这一途径,我们证明了已验证的和新的II类微球蛋白在肠杆菌科内外都广泛存在,这在以前还没有系统地显示过。观察到的II类微球蛋白的流行表明它们具有重要的生态意义,而新的微球蛋白的阐明为我们提供了一个资源,可以用来扩大我们对微球蛋白作为抗菌药物的结构和功能的认识。
Microcins are a class of antimicrobial peptides produced by certain Gram-negative bacterial species to kill or inhibit the growth of competing bacteria. Only 10 unique, experimentally validated class II microcins have been identified, and the majority of these come from Escherichia coli. Although the current representation of microcins is sparse, they exhibit a diverse array of molecular functionalities, uptake mechanisms, and target specificities. This broad diversity from such a small representation suggests that microcins may have untapped potential for bioprospecting peptide antibiotics from genomic data sets. We used a systematic bioinformatics approach to search for verified and novel class II microcins in E. coli and other species within its family, Enterobacteriaceae. Nearly one-quarter of the E. coli genome assemblies contained one or more microcins, where the prevalence of hits to specific microcins varied by isolate phylogroup. E. coli isolates from human extraintestinal and poultry meat sources were enriched for microcins, while those from freshwater were depleted. Putative microcins were found in various abundances across all five distinct phylogenetic lineages of Enterobacteriaceae, with a particularly high prevalence in the “Klebsiella” clade. Representative genome assemblies from species across the Enterobacterales order, as well as a few outgroup species, also contained putative microcin sequences. This study suggests that microcins have a complicated evolutionary history, spanning far beyond our limited knowledge of the currently validated microcins. Efforts to functionally characterize these newly identified microcins have great potential to open a new field of peptide antibiotics and microbiome modulators and elucidate the ways in which bacteria compete with each other. IMPORTANCE Class II microcins are small bacteriocins produced by strains of Gram-negative bacteria in the Enterobacteriaceae. They are generally understood to play a role in interbacterial competition, although direct evidence of this is limited, and they could prove informative in developing new peptide antibiotics. However, few examples of verified class II microcins exist, and novel microcins are difficult to identify due to their sequence diversity, making it complicated to study them as a group. Here, we overcome this limitation by developing a bioinformatics pipeline to detect microcins in silico. Using this pipeline, we demonstrate that both verified and novel class II microcins are widespread within and outside the Enterobacteriaceae, which has not been systematically shown previously. The observed prevalence of class II microcins suggests that they are ecologically important, and the elucidation of novel microcins provides a resource that can be used to expand our knowledge of the structure and function of microcins as antibacterials.
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