Rooney James, Rivera-de-Torre Esperanza, Li Ruizhe, Mclean Kevin, Price Daniel R G, Nisbet Alasdair J, Laustsen Andreas H, Jenkins Timothy P, Hofmann Andreas, Bakshi Somenath, Zarkan Ashraf, Cantacessi Cinzia
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Comput Struct Biotechnol J. 2024 Apr 10;23:1522-1533. doi: 10.1016/j.csbj.2024.04.019. eCollection 2024 Dec.
The complex relationships between gastrointestinal (GI) nematodes and the host gut microbiota have been implicated in key aspects of helminth disease and infection outcomes. Nevertheless, the direct and indirect mechanisms governing these interactions are, thus far, largely unknown. In this proof-of-concept study, we demonstrate that the excretory-secretory products (ESPs) and extracellular vesicles (EVs) of key GI nematodes contain peptides that, when recombinantly expressed, exert antimicrobial activity in vitro against . In particular, using time-lapse microfluidics microscopy, we demonstrate that exposure of to a recombinant saposin-domain containing peptide from the 'brown stomach worm', , and a metridin-like ShK toxin from the 'barber's pole worm', , results in cell lysis and significantly reduced growth rates. Data from this study support the hypothesis that GI nematodes may modulate the composition of the vertebrate gut microbiota directly via the secretion of antimicrobial peptides, and pave the way for future investigations aimed at deciphering the impact of such changes on the pathophysiology of GI helminth infection and disease.
胃肠道（GI）线虫与宿主肠道微生物群之间的复杂关系已被认为与蠕虫病和感染结果的关键方面有关。然而，迄今为止，控制这些相互作用的直接和间接机制在很大程度上仍不清楚。在这项概念验证研究中，我们证明了关键胃肠道线虫的排泄-分泌产物（ESPs）和细胞外囊泡（EVs）含有肽，当这些肽重组表达时，在体外对……具有抗菌活性。特别是，使用延时微流控显微镜，我们证明将……暴露于来自“棕色胃虫”（奥斯特线虫）的含鞘脂激活蛋白域的重组肽和来自“捻转血矛线虫”的类海葵毒素样ShK毒素会导致细胞裂解并显著降低生长速率。这项研究的数据支持了这样一种假设，即胃肠道线虫可能通过分泌抗菌肽直接调节脊椎动物肠道微生物群的组成，并为未来旨在破译此类变化对胃肠道蠕虫感染和疾病病理生理学影响的研究铺平了道路。
