Buzy Armelle, Allain Camille, Harrington John, Lesuisse Dominique, Mikol Vincent, Bruhn David F, Maule Aaron G, Guillemot Jean-Claude
Sanofi R&D, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin, France.
Boehringer Ingelheim Animal Health, Duluth, Georgia 30096, United States.
ACS Omega. 2021 Apr 7;6(15):10288-10305. doi: 10.1021/acsomega.1c00650. eCollection 2021 Apr 20.
The nematode (the barber's pole worm) is an endoparasite infecting wild and domesticated ruminants worldwide. Widespread anthelmintic resistance of requires alternative strategies to control this parasite. Neuropeptide signaling represents a promising target for anthelmintic drugs. Identification and relative quantification of nematode neuropeptides are, therefore, required for the development of such therapeutic targets. In this work, we undertook the profiling of the whole larvae at different stages for the direct sequencing of the neuropeptides expressed at low levels in these tissues. We set out a peptide extraction protocol and a peptidomic workflow to biochemically characterize bioactive peptides from both first-stage (L1) and third-stage larvae (L3) of . This work led to the identification and quantification at the peptidomic level of more than 180 mature neuropeptides, including amidated and nonamidated peptides, arising from 55 precursors of . The differential peptidomic approach provided evidence that both life stages express most FMRFamide-like peptides (FLPs) and neuropeptide-like proteins (NLPs). The peptidome resource, established in this work, could add the discovery of neuropeptide system-targeting drugs for ruminants.
线虫（捻转血矛线虫）是一种体内寄生虫，感染全球范围内的野生和家养反刍动物。广泛存在的驱虫抗性需要替代策略来控制这种寄生虫。神经肽信号传导是驱虫药物的一个有前景的靶点。因此，为了开发此类治疗靶点，需要对线虫神经肽进行鉴定和相对定量。在这项工作中，我们对不同阶段的整个幼虫进行了分析，以便对这些组织中低水平表达的神经肽进行直接测序。我们制定了一种肽提取方案和一种肽组学工作流程，以从捻转血矛线虫的第一阶段幼虫（L1）和第三阶段幼虫（L3）中对生物活性肽进行生化表征。这项工作导致在肽组学水平上鉴定和定量了180多种成熟神经肽，包括来自捻转血矛线虫55种前体的酰胺化和非酰胺化肽。差异肽组学方法提供了证据，表明两个生命阶段都表达大多数FMRF酰胺样肽（FLP）和神经肽样蛋白（NLP）。在这项工作中建立的捻转血矛线虫肽组资源可能会增加针对反刍动物的神经肽系统靶向药物的发现。
