Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm
Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm
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DOI：
10.3389/fimmu.2020.01873
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发表时间：
2020-09
影响因子：
7.3
通讯作者：
N. Yount;D. C. Weaver;J. de Anda;Ernest Y Lee;Michelle W. Lee;G. Wong;M. Yeaman
中科院分区：
文献类型：
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作者：
N. Yount;D. C. Weaver;J. de Anda;Ernest Y Lee;Michelle W. Lee;G. Wong;M. Yeaman
抗菌化合物最初出现在原核生物中，是出于竞争性自卫的需要。从这个角度来看，原核生物发明了第一个宿主防御肽。这些肽中最具特征的是II类细菌素，主要由革兰氏阳性细菌产生的核糖体合成的多肽。在目前的研究中，创建了一个张量搜索协议- baciα算法-以高保真度识别和分类细菌素序列。baciα算法在高维查询工具中集成了共识签名序列，物理化学和基因组模式元素，以选择细菌素样肽。它准确地检索和区分了几乎所有已知的II类细菌素家族，特异性为86%。此外，该算法检索了大量未预见的假定细菌素肽序列。最近开发的机器学习分类器预测绝大多数检索到的序列在目标膜中诱导负高斯曲率，这是抗菌活性的标志。合成了候选细菌素的原型序列，并在体外对广泛的人类病原体显示出强大的抗菌功效。因此，baci α算法扩展了原核宿主防御细菌素的范围，并实现了一种创新的生物信息学发现策略。了解原核生物如何在千万年的时间里保护自己免受微生物的威胁，有望发现新的抗感染策略，以应对现代抗生素耐药性的挑战。
Antimicrobial compounds first arose in prokaryotes by necessity for competitive self-defense. In this light, prokaryotes invented the first host defense peptides. Among the most well-characterized of these peptides are class II bacteriocins, ribosomally-synthesized polypeptides produced chiefly by Gram-positive bacteria. In the current study, a tensor search protocol—the BACIIα algorithm—was created to identify and classify bacteriocin sequences with high fidelity. The BACIIα algorithm integrates a consensus signature sequence, physicochemical and genomic pattern elements within a high-dimensional query tool to select for bacteriocin-like peptides. It accurately retrieved and distinguished virtually all families of known class II bacteriocins, with an 86% specificity. Further, the algorithm retrieved a large set of unforeseen, putative bacteriocin peptide sequences. A recently-developed machine-learning classifier predicted the vast majority of retrieved sequences to induce negative Gaussian curvature in target membranes, a hallmark of antimicrobial activity. Prototypic bacteriocin candidate sequences were synthesized and demonstrated potent antimicrobial efficacy in vitro against a broad spectrum of human pathogens. Therefore, the BACIIα algorithm expands the scope of prokaryotic host defense bacteriocins and enables an innovative bioinformatics discovery strategy. Understanding how prokaryotes have protected themselves against microbial threats over eons of time holds promise to discover novel anti-infective strategies to meet the challenge of modern antibiotic resistance.