Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.

Biomphalaria spp. serve as obligate intermediate hosts for the human blood fluke Schistosoma mansoni. Following S. mansoni penetration of Biomphalaria glabrata, hemocytes of resistant snails migrate towards the parasite, encasing the larva in a multicellular capsule resulting in its destruction via a cytotoxic reaction. Recent studies have revealed the importance of hydrogen peroxide and nitric oxide (H 2 O 2 , NO) in parasite killing [1,2]. It is assumed H 2 O 2 and NO production is tightly regulated although the specific molecules involved remain largely unknown. Consequently, the potential role of cell signaling pathways in B. glabrata hemocyte H 2 O 2 production was investigated by evaluating the effects of specific inhibitors of selected signaling proteins. Results suggest that both ERK and p38 MAPKs are involved in the regulation of B. glabrata H 2 O 2 release in response to stimulation by PMA and galactose-conjugated BSA. However, the involvement of the signaling proteins PKC, PI 3 kinase and PLA 2 differs between PMA-and BSA-gal-induced H 2 O 2 production.

The blood flukes Schistosoma mansoni and Schistosoma japonicum inflict immense suffering as agents of human schistosomiasis. Previous investigations have found the nervous systems of these worms contain abundant immunoreactivity to antisera targeting invertebrate neuropeptide Fs (NPFs) as well as structurally similar neuropeptides of the mammalian neuropeptide Y (NPY) family. Here, cDNAs encoding NPF in these worms were identified, and the mature neuropeptides from the two species differed by only a single amino acid. Both neuropeptides feature the characteristics common among NPFs; they are 36 amino acids long with a carboxyl-terminal Gly-Arg-X-Arg-Phe-amide and Tyr residues at positions 10 and 17 from the carboxyl terminus. Synthetic S. mansoni NPF potently inhibits the forskolin-stimulated accumulation of cAMP in worm homogenates, with significant effects at 10 ؊11 M. This is the first demonstration of an endogenous inhibition of cAMP by an NPF, and because this is the predominant pathway associated with vertebrate NPY family peptides, it demonstrates a conservation of downstream signaling pathways used by NPFs and NPY peptides.Blood fluke parasites of the genus Schistosoma are the most important metazoan parasites of humans and are the etiological agents of schistosomiasis (bilharzia), which afflicts over 200 million people. Schistosomiasis ranks second, behind only malaria, in terms of its overall negative socio-economic and public health impact on the tropical and subtropical world, and it remains among the top five disease priorities of the World Health Organization (WHO) 1 (1). Control of the disease rests almost solely on chemotherapy using the anthelmintic praziquantel (2-4). Most disturbingly, the long term utility of praziquantel has been brought into question because of growing reports of infections not responding to the recommended dosage (5-8) and worms with decreased sensitivity (9, 10). WHO has accordingly identified research into the basic biology of schistosomes as a priority, with the hope of identifying targets for the next generation of antischistosomal drugs (1).Schistosomes belong to the class Trematoda of the phylum Platyhelminthes (flatworms) and, as such, are among the simplest extant animals to display brain development with the concomitant distinction between central and peripheral neuronal elements. One distinct feature of platyhelminths and other early diverging phyla is a prominent peptidergic component within their nervous systems. One family of neuropeptides abundant among these early animals is the neuropeptide F (NPF) family (11-14). NPFs are 36 -40-amino acid peptides featuring a carboxyl-terminal Gly-Arg-X-Arg-Phe-amide (GRXRF-NH 2 ) motif and tyrosine residues at positions 10 and 17 relative to the carboxyl terminus.These characteristics are common to those of vertebrate NPY family peptides, 36 amino acid neuropeptides with RXR(F/Y)-NH 2 carboxyl termini, Tyr residues at positions 10 and 17 relative to the carboxyl termini, and prolines in a PXXPXXP motif near the amino ter...

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Although the effects of trematode infection on snail host physiology or host responses on parasite development have been well described in the literature, very little is known regarding the underlying mechanisms and specific molecules responsible for mediating those effects. It is presumed that many host-parasite interactions are communicated through receptor-mediated events, in particular those involving haemocytic immune responses to invading parasites, larval motility and migration through host tissues, and larval acquisition of host molecules either as nutrients or critical developmental factors. The intent of this chapter is to review current knowledge of molecules (both receptors and their ligands or counter-receptors) involved in molecular communication at the interface between larval trematodes, especially the mother or primary sporocyst stage, and host cells/tissues in intimate proximity to developing larvae. Information to date suggests that the molecular exchange at this interface is a highly complex and dynamic process, and appears to be regulated in specific cases. Topics discussed will focus on snail cell receptor interactions with the sporocyst tegument and its secretions, host cell-cell and cell-substrate adhesion receptors and their related signal transduction pathways, and sporocyst tegumental surface receptors and ligands involved in the binding of soluble host molecules.