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

Abstract

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.

Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?

“…In helminths, studies have focused primarily on Schistosoma and Brugia . In these parasites, AMPs have effects on motility, development, egg deposition, and the integumentary surface [ 136 , 137 , 138 , 139 , 140 ]. In Brugia pahangi , synthetic cecropins A/B, AMPs from insect hemolymph, attenuate microfilariae mobility and larval development in adult female Aedes aegypti [ 136 ].…”

“…In S. mansoni , an AMP called schistocins has been obtained from the protein SmKI-1, a key protein for the survival of this nematode, which has activity against Schistosoma itself [ 142 ]. Likewise, putative neuropeptides derived from this parasite alter the behavior of the cercariae stage, therefore their use has been proposed as strategy for the control of the infection [ 140 ].…”