A Biomphalaria glabrata peptide that stimulates significant behaviour modifications in aquatic free-living Schistosoma mansoni miracidia

The human disease schistosomiasis (or bilharzia) is caused by the helminth blood fluke parasite Schistosoma mansoni, which requires an intermediate host, the freshwater gastropod snail Biomphalaria glabrata (the most common intermediate host). The free-swimming parasite miracidia utilises an excellent chemosensory sense to detect and locate an appropriate host. This study investigated the biomolecules released by the snail that stimulate changes in the behaviour of the aquatic S. mansoni miracidia. To achieve this, we have performed an integrated analysis of the snail-conditioned water, through chromatography and bioassay-guided behaviour observations, followed by mass spectrometry. A single fraction containing multiple putative peptides could stimulate extreme swimming behaviour modifications (e.g. velocity, angular variation) similar to those observed in response to crude snail mucus. One peptide (P12;R-DITSGLDPEVADD-KR) could replicate the stimulation of miracidia behaviour changes. P12 is derived from a larger precursor protein with a signal peptide and multiple dibasic cleavage sites, which is synthesised in various tissues of the snail, including the central nervous system and foot. P12 consists of an alpha helix secondary structure as indicated by circular dichroism spectroscopy. This information will be helpful for the development of approaches to manipulate this parasites life cycle, and opens up new avenues for exploring other parasitic diseases which have an aquatic phase using methods detailed in this investigation. Author summary In aquatic environments, where the vast majority of animals live in darkness, key relationships are often formed and maintained by chemical communication (including smell and taste). Parasites with an aquatic life phase rely on an exquisite sense of chemosensation to detect host biomolecules (kairomones), allowing them to locate and infect their host. Our study identifies the first kairomone released by the freshwater gastropod snail Biomphalaria glabrata, an intermediate host for the helminth blood fluke parasite Schistosoma mansoni. This is a key aspect of the S. mansoni life-cycle that ultimately leads to human infection, causing the disease schistosomiasis (or bilharzia), which is considered the most devastating human helminth infection in terms of global morbidity and mortality. The kairomone we identify is a peptide that does not appear to share any similarity with any other known animal peptide. This information will be helpful as we explore methods to interrupt parasite infection, and therefore break the cycle of infection that causes a major human disease.