Analysis of rhodopsin G protein-coupled receptor orthologs reveals semiochemical peptides for parasite (Schistosoma mansoni) and host (Biomphalaria glabrata) interplay

Abstract

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.

Identification of Schistosoma mansoni miracidia attractant candidates in infected Biomphalaria glabrata using behaviour-guided comparative proteomics

“…Nevertheless, proteins associated with reproduction have been implicated in inducing behaviour change in miracidia. An example is the B. glabrata buccalin peptide ( 21 ), a miracidia attractant known to play a role in reproduction in snails (and other molluscs) ( 68 , 69 ). This suggests that sex-related chemicals may be a contributing factor to miracidia attraction; however, the snails likely release several other attractants unrelated to reproduction.…”

“…One such attractant peptide is P12 (—R- DITSGLDPEVADD -KR—), which is highly expressed in the central nervous system, foot, heart and kidney and produced identical changes in miracidia behaviour to naïve (uninfected) B. glabrata SCW ( 20 ). However, aside from P12, few attraction chemicals have been identified ( 21 ). Comparative analyses of the chemical composition of attractive and non-attractive SCW may enable the identification of S. mansoni miracidia attractants in the former.…”

The FMRF-NH2 gated sodium channel of Biomphalaria glabrata: Localization and expression following infection by Schistosoma mansoni

“…In common with most neuropeptides, the gastropod FMRF-NH 2 -related peptides (FaRPs) activate G-protein coupled receptors (GPCRs) that regulate ion channels via second messenger systems [ 20 , 21 , 22 , 23 ]. In addition, FMRF-NH 2 directly activates a member of the degenerin / epithelial sodium channel (DEG/ENaC) superfamily of channels that do not require second messenger signaling [ 24 , 25 , 26 , 27 ].…”

The FMRF-NH2Gated Sodium Channel ofBiomphalaria glabrata: Localization and Expression Following Infection bySchistosoma mansoni

“…The copyright holder for this preprint this version posted December 15, 2022. ; https://doi.org/10.1101/2022.12.15.520648 doi: bioRxiv preprint 4 (Higgins et al 1978;Piomelli et al 1987;Willoughby et al 1999a, b;Phan et al 2022). In addition, FMRF-NH2 directly activates a member of the degenerin / epithelial sodium channel (DEG/ENaC) superfamily of channels that do not require second messenger signaling (Green et al 1994;Lingueglia et al 1995Lingueglia et al , 2006Cottrell 1997).…”

“…In common with most neuropeptides, the gastropod FMRF-NH2-related peptides activate Gprotein coupled receptors (GPCRs) that regulate ion channels via second messenger systems (Higgins et al 1978;Piomelli et al 1987;Willoughby et al 1999a, b;Phan et al 2022). In addition, FMRF-NH2 directly activates a member of the degenerin / epithelial sodium channel (DEG/ENaC) superfamily of channels that do not require second messenger signaling (Green et al 1994;Lingueglia et al 1995Lingueglia et al , 2006Cottrell 1997).…”