SUMMARY
The evolutionary success of parasitoid wasps, a highly diverse group of
insects widely used in biocontrol, depends on a variety of life history
strategies in conflict with those of their hosts [1]. Drosophila melanogaster
is a natural host of parasitic wasps of the genus Leptopilina.
Attack by L. boulardi (Lb), a specialist wasp
to flies of the melanogaster group, activates NF-κB-mediated humoral and
cellular immunity. Inflammatory blood cells mobilize and encapsulate
Lb eggs and embryos [2–5].
L. heterotoma (Lh), a generalist wasp,
kills larval blood cells and actively suppresses immune responses. Spiked
virus-like particles (VLPs) in wasp venom have clearly been linked to its
successful parasitism of Drosophila [6], but VLP composition and their biotic
nature have remained mysterious. Our proteomics studies reveal that VLPs lack
viral coat proteins but possess a pharmacopoeia of (a) eukaryotic vesicular
transport system, (b) immunity, and (c) previously unknown proteins. These novel
proteins distinguish Lh from Lb VLPs; notably,
some proteins specific to Lh VLPs possess sequence similarities
with bacterial secretion system proteins. Structure-informed analyses of an
abundant Lh VLP surface/spike-tip protein, p40, reveal
similarities to the needle-tip invasin proteins SipD/IpaD of Gram negative
bacterial type 3 secretion systems that breach immune barriers and deliver
virulence factors into mammalian cells. Our studies suggest that
Lh VLPs represent a new class of extracellular organelles
and share pathways for protein delivery with both eukaryotic microvesicles and
bacterial surface secretion systems. Given their mixed prokaryotic/eukaryotic
properties, we propose the term Mixed Strategy Extracellular Vesicles (MSEVs) to
replace VLP.