Novel Organelles with Elements of Bacterial and Eukaryotic Secretion Systems Weaponize Parasites of Drosophila

Mary Ellen Heavner, Johnny Ramroop, Gwenaelle Gueguen, Girish Ramrattan, Georgia Dolios, Michael Scarpati, Jonathan Kwiat, Sharmila Bhattacharya, Rong Wang, Shaneen Singh, Shubha Govind

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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 wasps’ successful parasitism of Drosophila [6], but the composition of VLPs and their biotic nature have remained mysterious. Our proteomics studies reveal that VLPs lack viral coat proteins but possess a pharmacopoeia of (1) the eukaryotic vesicular transport system, (2) immunity, and (3) 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 and spike-tip protein, p40, reveal similarities to the needle-tip invasin proteins SipD and 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 and eukaryotic properties, we propose the term mixed-strategy extracellular vesicle (MSEV) to replace VLP. Heavner et al. report the non-viral composition of mixed-strategy extracellular vesicles (MSEVs), previously known as virus-like particles. MSEVs mediate parasitic success of Leptopilina heterotoma against their fly hosts. The authors describe sequences with eukaryotic microvesicluar signature, prokaryotic-like proteins, and a new class of GTPases.

Original languageEnglish
Pages (from-to)2869-2877.e6
JournalCurrent Biology
Issue number18
StatePublished - 25 Sep 2017
Externally publishedYes


  • Drosophila
  • T3 secretion system
  • hemocytes
  • immune suppression
  • mixed-strategy extracellular vesicles
  • parasitoid wasps
  • proteomics
  • secretion systems
  • venom
  • virus-like particles


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