Nematode parasite infections cause disease in humans and animals and threaten global food security by reducing productivity in livestock and crop farming. The escalation of anthelmintic resistance in economically important nematode parasites underscores the need for the identification of novel drug targets in these worms. Nematode neuropeptide signalling is an attractive system for potential chemotherapeutic exploitation, with neuropeptide G-protein coupled receptors (NP-GPCRs) representing the leading target candidates therein. In order to successfully validate NP-GPCRs as targets for parasite control it is necessary to characterise their function and importance to nematode biology. This can be aided through identifying receptor activating ligand(s) in a process known as receptor deorphanisation. Such efforts first require the identification of all neuropeptide ligands within parasites. Here we comb the genomes of nine therapeutically relevant pathogenic nematode species to comprehensively characterise the nematode parasite neuropeptide-like protein (NLP) complements, and details the discovery of several previously unreported, yet conserved, neuropeptides and neuropeptide-encoding genes. We identify the neuropeptides that are most highly conserved in all parasites examined, and characterise their physiological activity on the reproductive musculature of the parasite, Ascaris suum. These data suggest conserved neuropeptide functions in both free living and parasitic nematodes, and support the potential for exploitation of the neuropeptide signalling system as an anthelmintic target.

中文翻译：

---

寄生线虫中神经肽样蛋白（NLP）谱的计算机分析

线虫寄生虫感染通过降低畜牧业和农作物的生产力，导致人畜共患疾病，并威胁全球粮食安全。在经济上重要的线虫寄生虫中，驱虫药耐药性的升高凸显了对这些蠕虫中新型药物靶标的识别需求。线虫神经肽信号传导是潜在的化学疗法开发的诱人系统，其中神经肽G蛋白偶联受体（NP-GPCR）代表其中的主要靶标候选物。为了成功验证NP-GPCR作为寄生虫控制的靶标，有必要表征其功能和对线虫生物学的重要性。这可以通过在称为受体去孤儿化的过程中鉴定受体活化配体来辅助。这种努力首先需要鉴定寄生虫内的所有神经肽配体。在这里，我们梳理了九种与治疗相关的致病线虫物种的基因组，以全面表征线虫寄生虫神经肽样蛋白（NLP）补体，并详细介绍了一些以前未报道但仍保守的神经肽和神经肽编码基因的发现。我们确定在所有检查到的寄生虫中最高度保守的神经肽，并表征它们对寄生虫A虫的繁殖肌肉组织的生理活性。这些数据表明在自由的生活和寄生线虫中保守的神经肽功能，并支持利用神经肽信号系统作为驱虫目标的潜力。在这里，我们梳理了九种与治疗相关的致病线虫物种的基因组，以全面表征线虫寄生虫神经肽样蛋白（NLP）补体，并详细介绍了一些以前未报道但仍保守的神经肽和神经肽编码基因的发现。我们确定在所有检查到的寄生虫中最高度保守的神经肽，并表征它们对寄生虫A虫的繁殖肌肉组织的生理活性。这些数据表明在自由的生活和寄生线虫中保守的神经肽功能，并支持利用神经肽信号系统作为驱虫目标的潜力。在这里，我们梳理了九种与治疗相关的致病线虫物种的基因组，以全面表征线虫寄生虫神经肽样蛋白（NLP）补体，并详细介绍了一些以前未报道但仍保守的神经肽和神经肽编码基因的发现。我们确定在所有检查到的寄生虫中最高度保守的神经肽，并表征它们对寄生虫A虫的繁殖肌肉组织的生理活性。这些数据表明在自由的生活和寄生线虫中保守的神经肽功能，并支持利用神经肽信号系统作为驱虫目标的潜力。