# Venomous Cargo: Diverse Toxin-Related Proteins Are Associated with Extracellular Vesicles in Parasitoid Wasp Venom

## TL;DR

Parasitoid wasp venom contains extracellular vesicles with toxin-related proteins that suppress host defenses, potentially delivering virulence factors to the host.

## Contribution

Discovery of conserved extracellular vesicle markers and toxin-like proteins in parasitoid wasp venom proteomes, suggesting a novel mechanism of parasitism.

## Key findings

- Venom particles from Leptopilina wasps contain extracellular vesicle markers and toxin-related proteins.
- Both L. boulardi and L. heterotoma venom proteomes show enrichment in endomembrane and exosomal components.
- Uncharacterized proteins with structural similarity to ADP-ribosyltransferase enzymes were identified in venom.

## Abstract

Unusual membrane-bound particles are present in the venom of the parasitoid wasps that parasitize Drosophila melanogaster. These venom particles harbor about 400 proteins and suppress the encapsulation of a wasp egg. Whereas the proteins in the particles of Leptopilina boulardi venom modify host hemocyte properties, those in L. heterotoma kill host hemocytes. The mechanisms underlying this differential effect are not well understood. The proteome of the L. heterotoma venom particles has been described before, but that of L. boulardi has not been similarly examined. Using sequence-based programs, we report the presence of conserved proteins in both proteomes with strong enrichment in the endomembrane and exosomal cell components. Extracellular vesicle markers are present in both proteomes, as are numerous toxins. Both proteomes also contain proteins lacking any annotation. Among these, we identified the proteins with structural similarity to the ADP-ribosyltransferase enzymes involved in bacterial virulence. We propose that invertebrate fluids like parasitoid venom contain functional extracellular vesicles that deliver toxins and virulence factors from a parasite to a host. Furthermore, the presence of such vesicles may not be uncommon in the venom of other animals. An experimental verification of the predicted toxin functions will clarify the cellular mechanisms underlying successful parasitism.