Molecular Determinants and Behavioral Fingerprints of Schistosome Miracidia Host-Seeking - Schistosomiasis is a disease caused by chronic infections of human schistosomes, parasitic flatworms that are transmitted by aquatic snails. Schistosomes cause disease in over 250 million people but has been designated as a Neglected Tropical Disease because of the outsized disease burden in comparison to the investment given to it by the global health community. Schistosomiasis is controlled primarily by mass drug administration (MDA) to people living in endemic areas. Though MDA has had incredible success in reducing the burden of disease, many locations exist where schistosome prevalence remains high despite repeated MDA with high coverage. In these cases, the stakeholders are encouraged to implement snail control through chemical molluscicide treatment of local waters. Chemical molluscicides are effective but can have harmful ecological consequences by eliminating target snails and, at times, off-target invertebrates and plants. New strategies could be developed that reduce the density of infected snails without reducing populations of snails themselves. Miracidia, the aquatic snail-infective stage of schistosomes, utilize a variety of sensory modalities during host-seeking (i.e., geosensation, photosensation, and chemosensation), resulting in accumulation near potential snail hosts. Once a miracidium enters the active space of a snail – the area in which it can sense snail chemical cues – it undergoes a distinct behavioral transition that results in contact with the snail. The host-seeking and penetration behaviors have been qualitatively described by careful observation, but quantitative models of these behaviors have yet to be generated, making them difficult to experimentally interrogate. Further, though a variety of circumstantial evidence exists that supports a secreted glycosylated peptide as the primary snail cue sensed by miracidia, this has not been confirmed in vivo. This project will seek to quantitatively describe miracidia behaviors in the presence and absence of snails and extract behavioral fingerprints from high-resolution tracking data generated from a unique, bespoke recording device with a large field of view. Behavioral fingerprints and an optimized high-throughput experimental approach will set a foundation for screening of environmental stimuli and small molecules for inhibitory effects on miracidia sensation of snail cues. In parallel, the snail secreted peptide that is hypothesized to stimulate miracidia accumulation will be validated in vivo, and a comparative approach using new genomic reference data from several schistosome snail hosts will explore this critical host-parasite interaction among three 4 snail species and 2 schistosome species. These comparisons will allow for the generation of a consensus sequence for the stimulatory peptide, which could act as a scaffold for future optimization for activity on miracidia.
