Genomic and transcriptional analysis of genes containing fibrinogen and IgSF domains in the schistosome vector Biomphalaria glabrata, with emphasis on the differential responses of snails susceptible or resistant to Schistosoma mansoni

Achieving a deeper understanding of the factors controlling the defense responses of invertebrate vectors to the human-infecting pathogens they transmit will provide needed new leads to pursue for control. Consequently, we provide new genomic and transcriptomic insights regarding FReDs (containing a fibrinogen domain) and FREPs (fibrinogen domain and one or two IgSF domains) from the planorbid snailBiomphalaria glabrata, a Neotropical vector ofSchistosoma mansoni, causative agent of human intestinal schistosomiasis. Using new bioinformatics approaches to improve annotation applied to both genome and RNA-Seq data, we identify 73 FReD genes, 39 of which are FREPs. We provide details of domain structure and consider relationships and homologies ofB.glabrataFBG and IgSF domains. We note that schistosome-resistant (BS-90) snails mount complex FREP responses following exposure toS.mansoniinfection whereas schistosome-susceptible (M line) snails do not. We also identify several coding differences between BS-90 and M line snails in three FREPs (2, 3.1 and 3.2) repeatedly implicated in other studies of anti-schistosome responses. In combination with other results, our study provides a strong impetus to pursue particular FREPs (2, 3.1, 3.2 and 4) as candidate resistance factors to be considered more broadly with respect to schistosome control efforts, including involving otherBiomphalariaspecies vectoringS.mansoniin endemic areas in Africa. Author summary Just as malaria parasites depend on mosquitoes for transmission,Schistosomatrematodes that infect 200+ million people in developing countries depend on freshwater snails to support their development. New control methods targeting schistosomes in the snail host are urgently needed to help break the cycle of transmission. Identification of molecules in snails that confer or facilitate resistance to successful larval development offers one way forward. Building on previous studies and new data, we used a combination of bioinformatics tools to characterize a repertoire of molecules inB.glabratacontaining fibrinogen or IgSF domains, or both (the latter molecules called FREPs, first discovered inB.glabrata). We found that snails resistant to schistosomes mount vigorous, multi-component FREP responses following exposure to schistosomes whereas responses of susceptible snails are modest by comparison. Furthermore, for four FREPs repeatedly implicated in snail responses to trematodes, three (FREPs 2, 3.1 and 3.2) exist in distinctive allelic forms in susceptible and resistant snails. We propose that the search for homologous molecules needs to move to the field, toB.glabratain the Neotropics and to other vector species ofBiomphalariain Africa, to explore the potential of FREPs as resistance factors worthy of development as control agents.