Parasitoid Jewel Wasp Mounts Multipronged Neurochemical Attack to Hijack a Host Brain

Abstract

In BriefProteomic analysis of Ampulex compressa venom reveals a multifaceted attack on the host central nervous system. Rather than inducing paralysis or cytotoxicity, the venom appears to modify endogenous signaling, rendering the host lethargic and compliant. Some peptides and proteins in the venom are in precursor form, only to be processed into fully active form once injected into the pH-neutral host brain. This analysis deepens mechanistic understanding of venom action and points to signaling systems previously unrecognized in regulation of locomotion. Graphical Abstract Highlights• The venom transcriptome and proteome (venome) of Ampulex compressa are reported.• 264 proteins (enzymes, peptides, neurotransmitters) were detected.• The venom contains unprocessed neuropeptide precursors absent mature peptides.• Neuropeptide precursors likely are processed into active form upon envenomation.The parasitoid emerald jewel wasp Ampulex compressa induces a compliant state of hypokinesia in its host, the American cockroach Periplaneta americana through direct envenomation of the central nervous system (CNS). To elucidate the biochemical strategy underlying venominduced hypokinesia, we subjected the venom apparatus and milked venom to RNAseq and proteomics analyses to construct a comprehensive "venome," consisting of 264 proteins. Abundant in the venome are enzymes endogenous to the host brain, including M13 family metalloproteases, phospholipases, adenosine deaminase, hyaluronidase, and neuropeptide precursors. The amphipathic, alpha-helical ampulexins are among the most abundant venom components. Also prominent are members of the Toll/NF-B signaling pathway, including proteases Persephone, Snake, Easter, and the Toll receptor ligand Spä tzle. We find evidence that venom components are processed following envenomation. The acidic (pHϳ4) venom contains unprocessed neuropeptide tachykinin and corazonin precursors and is conspicuously devoid of the corresponding processed, biologically active peptides. Neutralization of venom leads to appearance of mature tachykinin and corazonin, suggesting that the wasp employs precursors as a prolonged time-release strategy within the host brain post-envenomation. Injection of fully processed tachykinin into host cephalic ganglia elicits short-term hypokinesia. Ion channel modifiers and cytolytic toxins are absent in A. compressa venom, which appears to hijack control of the host brain by introducing a "storm" of its own neurochemicals. Our findings deepen understanding of the chemical warfare underlying host-parasitoid interactions and in particular neuromodulatory mechanisms that enable manipulation of host behavior to suit the nutritional needs of opportunistic parasitoid progeny.

Deadly Proteomes: A Practical Guide to Proteotranscriptomics of Animal Venoms

“…LC-MS/MS can be conducted with a variety of analyzers including the lower-massresolving ion trap and triple quadrupole instruments, intermediate resolving power quadrupole-quadrupole-TOF (QqTOF) instruments, and higher-resolving-power triple-quadropole-TOF (QqQ-TOF), Orbitrap or FT-ICR instruments. LC-MS/MS using DDA is the most common method for obtaining venom peptide fragmentation data in many laboratories, [22,25,[48][49][50][51][52]57,[65][66][67][68][69][70][71][72][73][74][75][76][77][78][79] including ours. [29,42,43,53,61,[80][81][82][83] These data are typically searched using an automated algorithm against a database of protein sequences to identify peptide primary structures.…”

“…The emPAI score is then calculated as 10 PAI -1 (or in a recent refinement, 6.5 PAI -1). [129] Arvidson et al [77] used emPAI, for example, to investigate the venom system of the jewel wasp Ampulex compressa, which injects venom into the brain of cockroaches to inhibit escape responses and convert them into "living larders" for their offspring. In this study, emPAI scores of toxins in extruded venom were compared to transcript abundances in the venom gland and the venom sac, which revealed that both of these structures in the venom apparatus contribute to venom secretion.…”

An economic dilemma between weapon systems may explain an arachno-atypical venom in wasp spiders (Argiope bruennichi)

“…ITP/CHH peptides have also been recruited into the venom systems of ticks and wasps and are not restricted to the HAND family. For example, emerald jewel wasp (Ampulex compressa) venom contains tachykinin and corazonin neuropeptides that induce hypokinesia in cockroaches (Arvidson et al, 2019), whereas exendin from the venom of helodermatid lizards is a modified glucagon-like peptide that interferes with pancreatic insulin release (Yap and Misuan, 2019). Amphibians have also recruited a variety of hormone peptides as skin toxins (Gaudino et al, 1985;Roelants et al, 2010;Roelants et al, 2013;Lüddecke et al, 2018).…”

Proteo-Transcriptomic Characterization of the Venom from the Endoparasitoid Wasp Pimpla turionellae with Aspects on Its Biology and Evolution

“…Nonetheless, more than 75% of known hymenopteran species are non-aculeate, i.e., are parasitoid wasps (parasitoids) that still utilize the ovipositor in its original function to lay eggs and "weaponize" it in a dual function to inject venom into host species they parasitize [8][9][10][11]. In stark contrast to aculeate venom, which is streamlined for defense to immobilize or to kill their prey [7,[12][13][14], venom of parasitoids mainly alters the physiology and behavior of the host to keep it alive while feeding the offspring [15][16][17][18][19]. Despite this interesting biology, only a few parasitoid venom systems were studied in more detail.…”

“…A prominent example is the jewel wasp Ampulex compressa that injects venom into the central nervous system of American cockroaches. The sting results in lethargy and hypokinesia accompanied by the suppression of any escape reflex without altering other behavior [19,23]. Proteomics analyses indicate that the neuropeptides tachykinin and corazonin induce these effects [19].…”