Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire.
Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire.
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DOI：
10.1371/journal.ppat.1011508
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发表时间：
2023-07
期刊：
影响因子：
6.7
通讯作者：
Mousley, Angela
中科院分区：
文献类型：
--
作者：
Irvine, Allister;Mckenzie, Darrin;McCoy, Ciaran J.;Graham, Robert L. J.;Graham, Ciaren;Huws, Sharon A.;Atkinson, Louise E.;Mousley, Angela
抗菌肽（Antimicrobial Peptides，AMP）是无脊椎动物先天免疫系统的关键组成部分，为病原微生物提供保护。寄生蠕虫（线虫门和扁形动物门）与其宿主和密切相关的微生物群有着复杂的相互作用，这些微生物群可能受到多种抗菌免疫效应物（包括AMP）的调控。蠕虫AMP的知识主要来自线虫，而扁形虫AMP库尚未被描述。这项研究强调了基于同源性的方法的局限性，用于识别推定的线虫AMP，用于表征扁形虫AMP，并揭示了创新的算法AMP预测方法提供了一种新的蠕虫AMP发现的替代策略。这里提供的数据：（i）揭示扁形虫不编码传统的钩轮藻AMP组（大防御素、CSαβ肽和Myticalin）;（ii）描述了用于发现新型蠕虫AMP的独特的集成计算管道;（iii）揭示了127种蠕虫物种中> 16，000种推定的AMP样肽;（iv）突出了富含半胱氨酸的肽主导蠕虫AMP样肽谱;（v）发现了八种具有不同抗菌活性的蠕虫AMP样肽，（vi）证明了猪蛔虫生物流体中AMP样肽的检测。这些数据代表了我们对假定的蠕虫AMP库的理解的重大进展，并强调了潜在的未开发的抗菌剂多样性来源，这可能为发现新型抗菌剂提供机会。此外，解开内源性蠕虫衍生的抗菌剂的作用及其影响宿主-蠕虫-微生物组相互作用的潜力可以用于开发独特的蠕虫控制方法。无脊椎动物抗微生物肽（AMP）是抵抗病原微生物的第一道防线。蠕虫是蠕虫（扁形虫，蛔虫），它们在整个生命周期中都生活在微生物丰富的环境中，但人们对它们如何保护自己免受病原体的侵害或如何与微生物相互作用知之甚少。了解蠕虫中的AMP概况，它们对蠕虫生物学的重要性，以及它们如何塑造微生物群落，可以揭示驱虫剂和/或抗菌剂开发的新方法。在这项研究中，我们描述了一种新的集成同源性和计算为基础的管道发现蠕虫AMP。这种方法表明，虽然扁形虫不具有传统的AMP，但它们具有主要富含半胱氨酸的独特AMP样肽的库。值得注意的是，使用该管道发现的八种新型蠕虫AMP样肽对一系列细菌具有抗菌活性，突出了它们作为新型抗菌剂的潜力。此外，肽组学分析表明猪蛔虫体液中存在AMP样肽，支持进一步研究这些肽及其在蠕虫中的功能的需要。这些数据提供了新的机会，以更好地了解蠕虫生物学，发现新的抗菌剂，并制定未来的蠕虫寄生虫控制策略。
Antimicrobial Peptides (AMPs) are immune effectors that are key components of the invertebrate innate immune system providing protection against pathogenic microbes. Parasitic helminths (phylum Nematoda and phylum Platyhelminthes) share complex interactions with their hosts and closely associated microbiota that are likely regulated by a diverse portfolio of antimicrobial immune effectors including AMPs. Knowledge of helminth AMPs has largely been derived from nematodes, whereas the flatworm AMP repertoire has not been described. This study highlights limitations in the homology-based approaches, used to identify putative nematode AMPs, for the characterisation of flatworm AMPs, and reveals that innovative algorithmic AMP prediction approaches provide an alternative strategy for novel helminth AMP discovery. The data presented here: (i) reveal that flatworms do not encode traditional lophotrochozoan AMP groups (Big Defensin, CSαβ peptides and Myticalin); (ii) describe a unique integrated computational pipeline for the discovery of novel helminth AMPs; (iii) reveal >16,000 putative AMP-like peptides across 127 helminth species; (iv) highlight that cysteine-rich peptides dominate helminth AMP-like peptide profiles; (v) uncover eight novel helminth AMP-like peptides with diverse antibacterial activities, and (vi) demonstrate the detection of AMP-like peptides from Ascaris suum biofluid. These data represent a significant advance in our understanding of the putative helminth AMP repertoire and underscore a potential untapped source of antimicrobial diversity which may provide opportunities for the discovery of novel antimicrobials. Further, unravelling the role of endogenous worm-derived antimicrobials and their potential to influence host-worm-microbiome interactions may be exploited for the development of unique helminth control approaches. Invertebrate antimicrobial peptides (AMPs) form the first line of defence against pathogenic microbes. Helminths are worms (flatworm, roundworm) that live in microbe-rich environments throughout their lifecycles, however little is known about how they protect themselves against pathogens or how they interact with microbes. Understanding AMP profiles in helminths, their importance to helminth biology, and how they shape microbial communities could reveal novel approaches for anthelmintic and/or antimicrobial development. In this study we describe a novel integrated homology- and computational-based pipeline for the discovery of helminth AMPs. This approach revealed that, whilst flatworms do not possess traditional AMPs, they have a repertoire of unique AMP-like peptides that are predominantly cysteine-rich. Significantly, eight novel helminth AMP-like peptides, discovered using this pipeline, have antibacterial activities against a range of bacteria highlighting their potential as novel antimicrobials. Further, peptidomics analyses demonstrate the presence of AMP-like peptides in Ascaris suum body fluid supporting the need to further characterise these peptides and their function(s) in helminths. These data present novel opportunities to better understand helminth biology, discover new antimicrobials, and develop future control strategies for helminth parasites.
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影响因子：
14.9
作者：
Blum M;Chang HY;Chuguransky S;Grego T;Kandasaamy S;Mitchell A;Nuka G;Paysan-Lafosse T;Qureshi M;Raj S;Richardson L;Salazar GA;Williams L;Bork P;Bridge A;Gough J;Haft DH;Letunic I;Marchler-Bauer A;Mi H;Natale DA;Necci M;Orengo CA;Pandurangan AP;Rivoire C;Sigrist CJA;Sillitoe I;Thanki N;Thomas PD;Tosatto SCE;Wu CH;Bateman A;Finn RD
通讯作者：
Finn RD
影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
14.9
作者：
Mistry J;Chuguransky S;Williams L;Qureshi M;Salazar GA;Sonnhammer ELL;Tosatto SCE;Paladin L;Raj S;Richardson LJ;Finn RD;Bateman A
通讯作者：
Bateman A
AMPEP：使用氨基酸特性和随机森林的分布模式对基于序列的抗菌肽的预测。
影响因子：
4.6
作者：
Bhadra P;Yan J;Li J;Fong S;Siu SWI
通讯作者：
Siu SWI
影响因子：
5.4
作者：
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通讯作者：
Zatylny-Gaudin C