Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore, QLD, 4558, Australia.
School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD, 4558, Australia.
Sci Rep. 2022 May 17;12(1):8243. doi: 10.1038/s41598-022-11996-x.
Schistosomiasis is a medically significant disease caused by helminth parasites of the genus Schistosoma. The schistosome life cycle requires chemically mediated interactions with an intermediate (aquatic snail) and definitive (human) host. Blocking parasite development within the snail stage requires improved understanding of the interactions between the snail host and the Schistosoma water-borne free-living form (miracidium). Innovations in snail genomics and aquatic chemical communication provide an ideal opportunity to explore snail-parasite coevolution at the molecular level. Rhodopsin G protein-coupled receptors (GPCRs) are of particular interest in studying how trematode parasites navigate towards their snail hosts. The potential role of GPCRs in parasites makes them candidate targets for new antihelminthics that disrupt the intermediate host life-cycle stages, thus preventing subsequent human infections. A genomic-bioinformatic approach was used to identify GPCR orthologs between the snail Biomphalaria glabrata and miracidia of its obligate parasite Schistosoma mansoni. We show that 8 S. mansoni rhodopsin GPCRs expressed within the miracidial stage share overall amino acid similarity with 8 different B. glabrata rhodopsin GPCRs, particularly within transmembrane domains, suggesting conserved structural features. These GPCRs include an orphan peptide receptor as well as several with strong sequence homologies with rhabdomeric opsin receptors, a serotonin receptor, a sulfakinin (SK) receptor, an allatostatin-A (buccalin) receptor and an FMRFamide receptor. Buccalin and FMRFa peptides were identified in water conditioned by B. glabrata, and we show synthetic buccalin and FMRFa can stimulate significant rates of change of direction and turn-back responses in S. mansoni miracidia. Ortholog GPCRs were identified in S. mansoni miracidia and B. glabrata. These GPCRs may detect similar ligands, including snail-derived odorants that could facilitate miracidial host finding. These results lay the foundation for future research elucidating the mechanisms by which GPCRs mediate host finding which can lead to the potential development of novel anti-schistosome interventions.
血吸虫病是一种由血吸虫属寄生虫引起的具有医学重要性的疾病。血吸虫的生命周期需要与中间宿主（水生蜗牛）和终宿主（人类）进行化学介导的相互作用。阻断蜗牛阶段的寄生虫发育需要更好地了解蜗牛宿主和血吸虫水生自由生活形式（尾蚴）之间的相互作用。蜗牛基因组学和水生化学通讯的创新为探索蜗牛-寄生虫在分子水平上的共同进化提供了理想的机会。视蛋白 G 蛋白偶联受体（GPCR）在研究吸虫寄生虫如何向其蜗牛宿主导航方面特别有趣。GPCR 在寄生虫中的潜在作用使它们成为候选靶标，用于新的抗寄生虫药物，这些药物可以破坏中间宿主的生命周期阶段，从而防止随后的人类感染。使用基因组生物信息学方法在蜗牛 Biomphalaria glabrata 和其专性寄生虫 Schistosoma mansoni 的尾蚴之间鉴定 GPCR 直系同源物。我们表明，在尾蚴阶段表达的 8 种 S. mansoni 视蛋白 GPCR 与 8 种不同的 B. glabrata 视蛋白 GPCR 具有总体氨基酸相似性，特别是在跨膜结构域内，表明存在保守的结构特征。这些 GPCR 包括一个孤儿肽受体以及几个与视紫红质 opsin 受体、5-羟色胺受体、磺胺素（SK）受体、阿特拉菌素-A（buccalin）受体和 FMRF 酰胺受体具有强序列同源性的受体。Buccalin 和 FMRFa 肽在 B. glabrata 调节的水中被鉴定出来，我们表明合成的 buccalin 和 FMRFa 可以刺激 S. mansoni 尾蚴显著改变方向和回头的反应速度。在 S. mansoni 尾蚴和 B. glabrata 中鉴定出直系同源 GPCR。这些 GPCR 可能检测到类似的配体，包括蜗牛来源的气味，可以促进尾蚴寻找宿主。这些结果为未来研究阐明 GPCR 介导宿主发现的机制奠定了基础，这可能导致新型抗血吸虫干预措施的潜在发展。
