Abstract

Helminths such as the blood fluke Schistosoma mansoni represent a major global health challenge due to limited availability of drugs. Most anthelminthic drug candidates are derived from plants, whereas insect-derived compounds have received little attention. This includes venom from assassin bugs, which contains numerous bioactive compounds. Here, we investigated whether venom from the European predatory assassin bug Rhynocoris iracundus has antischistosomal activity. Venom concentrations of 10–50 µg/mL inhibited the motility and pairing of S. mansoni adult worms in vitro and their capacity to produce eggs. We used EdU-proliferation assays to measure the effect of venom against parasite stem cells, which are essential for survival and reproduction. We found that venom depleted proliferating stem cells in different tissues of the male parasite, including neoblasts in the parenchyma and gonadal stem cells. Certain insect venoms are known to lyse eukaryotic cells, thus limiting their therapeutic potential. We therefore carried out hemolytic activity assays using porcine red blood cells, revealing that the venom had no significant effect at a concentration of 43 µg/mL. The observed anthelminthic activity and absence of hemolytic side effects suggest that the components of R. iracundus venom should be investigated in more detail as potential antischistosomal leads.

Highlights

  • Helminths infect more than 3.5 billion people worldwide, causing significant morbidity and economic losses [1,2]

  • The venom was tested for its anthelminthic activity against pairs of adult S. mansoni using an in vitro culture system over a period of 72 h

  • Given the abundance of spermatozoa in the lobes and seminal vesicle (Figure 6B) and the reduction of stem cell frequency and density, these results argue for the selective depletion of proliferating stem cells by assassin bug venom

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Summary

Introduction

Helminths (parasitic worms) infect more than 3.5 billion people worldwide, causing significant morbidity and economic losses [1,2]. Novel anthelminthic compounds are urgently needed to achieve better control of this important group of parasites given the limited availability of effective vaccines and drugs [3,4,5]. Blood flukes (schistosomes) such as Schistosoma mansoni cause schistosomiasis, a neglected tropical disease that globally affects more than 200 million people and causes 200,000 deaths each year [6,7]. The treatment of schistosomiasis currently relies on a limited. Antibiotics 2020, 9, 664 drug repertoire, with praziquantel as the current gold standard [9]. The discovery of alternative antischistosomal drugs is a high priority in neglected tropical disease research [13]

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