Identification of Putative Neuropeptides That Alter the Behaviour of Schistosoma mansoni Cercariae.

Abstract

Simple SummarySchistosoma mansoni is a common etiological agent of human schistosomiasis, one of the deadliest neglected tropical diseases in the developing world. Schistosoma neuropeptides have been considered a possible avenue of targeted biocontrol. We aimed to identify species-specific putative neuropeptides derived from the mammalian-infective stage, cercariae, which may function as biocontrol targets. A total of 11 neuropeptide precursors were identified for the first time in cercariae, all of which were highly specific to Schistosoma and many of which were highly expressed in the cercarial stage. We tested nine putative neuropeptides derived from these precursor proteins, three of which induced a significant increase in cercariae stopping, turning and passive behaviour over periods of both 1 min and 360 min post-exposure. These observations implicate the tested neuropeptides as involved in regulating cercarial behaviour. The characterisation of these putative neuropeptides may facilitate the innovation of biocontrols to prevent infection.Elucidating the infectivity of Schistosoma mansoni, one of the main etiological agents of human schistosomiasis, requires an improved understanding of the behavioural mechanisms of cercariae, the non-feeding mammalian infective stage. This study investigated the presence and effect of cercariae-derived putative neuropeptides on cercarial behaviour when applied externally. Cercariae were peptidomically analysed and 11 neuropeptide precursor proteins, all of which were specific to the Schistosoma genus and most of which highly expressed in the cercarial stage, were identified in cercariae for the first time. Protein–protein interaction analysis predicted the interaction of various neuropeptide precursors (e.g., Sm-npp-30, Sm-npp-33, Sm-npp-35) with cercarial structural proteins (e.g., myosin heavy chain and titin). In total, nine putative neuropeptides, selected based on their high hydrophobicity and small size (~1 kilodalton), were tested on cercariae (3 mg/mL) in acute exposure (1 min) and prolonged exposure (360 min) behavioural bioassays. The peptides AAYMDLPW-NH2, NRKIDQSFYSYY-NH2, FLLALPSP-OH, and NYLWDTRL-NH2 stimulated acute increases in cercarial spinning, stopping, and directional change during active states. However, only NRKIDQSFYSYY-NH2 caused the same behavioural changes at a lower concentration (0.1 mg/mL). After prolonged exposure, AAYMDLPW-NH2 and NYLWDTRL-NH2 caused increasing passive behaviour and NRKIDQSFYSYY-NH2 caused increasing body-first and head-pulling movements. These findings characterise behaviour-altering novel putative neuropeptides, which may inform future biocontrol innovations to prevent human schistosomiasis.