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Open AccessReview

Differential Properties of Venom Peptides and Proteins in Solitary vs. Social Hunting Wasps

Department of Agricultural Biology, Seoul National University, Seoul 151-921, Korea
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea
College of Pharmacy and Research Institute of Pharmaceutical Science, Gyeongsang National University, Jinju 660-701, Korea
Authors to whom correspondence should be addressed.
Academic Editor: Glenn F. King
Toxins 2016, 8(2), 32;
Received: 21 December 2015 / Revised: 13 January 2016 / Accepted: 14 January 2016 / Published: 22 January 2016
(This article belongs to the Special Issue Arthropod Venoms)


The primary functions of venoms from solitary and social wasps are different. Whereas most solitary wasps sting their prey to paralyze and preserve it, without killing, as the provisions for their progeny, social wasps usually sting to defend their colonies from vertebrate predators. Such distinctive venom properties of solitary and social wasps suggest that the main venom components are likely to be different depending on the wasps’ sociality. The present paper reviews venom components and properties of the Aculeata hunting wasps, with a particular emphasis on the comparative aspects of venom compositions and properties between solitary and social wasps. Common components in both solitary and social wasp venoms include hyaluronidase, phospholipase A2, metalloendopeptidase, etc. Although it has been expected that more diverse bioactive components with the functions of prey inactivation and physiology manipulation are present in solitary wasps, available studies on venom compositions of solitary wasps are simply too scarce to generalize this notion. Nevertheless, some neurotoxic peptides (e.g., pompilidotoxin and dendrotoxin-like peptide) and proteins (e.g., insulin-like peptide binding protein) appear to be specific to solitary wasp venom. In contrast, several proteins, such as venom allergen 5 protein, venom acid phosphatase, and various phospholipases, appear to be relatively more specific to social wasp venom. Finally, putative functions of main venom components and their application are also discussed.
Keywords: venom; solitary wasp; social wasp; peptide; protein; aculeata venom; solitary wasp; social wasp; peptide; protein; aculeata

1. Introduction

Wasps present an extremely diverse group in the suborder Apocrita (Hymenoptera), which is conventionally divided into two groups: Parasitica and Aculeata [1,2]. The clade Parasitica comprises the majority of parasitoid wasps, whereas the clade Aculeata contains most parasitic and predatory wasps with their ovipositor completely modified into a stinger for injecting venom [1]. These stinging Aculeata wasps are further divided into two subgroups (solitary vs. social) depending their lifestyle in the context of sociality [3].
Approximately 95% of 15,000 species of Aculeata wasps are solitary and are widely distributed across various families in the Aculeata [4]. The lifestyle of solitary wasps is unsocial; they do not form colonies [4]. After mating, the female solitary wasp builds one or more nests, hunts preys, and stores them in the cell(s) of the nest as provisions for the young.
Most solitary wasps sting their prey to paralyze and preserve it to use as food for the hatched wasp larvae. Thus, the primary compositions of the solitary wasp venom are various bioactive molecules that have the functions of paralysis, antimicrobial activity, developmental arrest, etc. Although the term “solitary wasp” is not strictly interchangeable with “hunting wasp”, the solitary wasp in this review refers to the aculeate wasps that hunt prey for offspring but are not social in their lifestyle. As expected from the common lifestyle, the primary purpose of ectoparasitoid venom is similar to that of solitary hunting wasp. The ectoparasitoid wasp venom is also known to contain a variety of bioactive substances that cause paralysis/lethargy and developmental arrest of the host (reviewed in [5]).
Carnivorous social wasps represent only a small portion in the Aculeata. Social wasps form colonies and some species, such as hornets and yellow jackets, build very large nests. Unlike solitary wasps, social wasps usually sting to defend themselves and their colonies from vertebrate predators [6]. Once disturbed, the entire colony is mobilized via an attack pheromone to sting the intruder, resulting in mass envenomation, which can be fatal [7]. Most social wasps generally butcher their prey, mostly insects and spiders, without stinging it and bring the most nourishing parts of it back to the colony to feed larvae [8]. Therefore, social wasps do not need to paralyze and preserve hunted prey with their venom. Social wasp’s venom appears to have evolved to maximize the defense potential in the ways to intensify venom-induced pain and/or to augment allergenic and immune responses of humans or animals [6]. Since social wasp venom contains various molecules that cause hypersensitivity reactions, such as anaphylaxis, it has been of a great medical and clinical importance.
Figure 1. Composite cladogram showing taxonomic relationship of Aculeata [2,8,9]. Sociality (solitary or social) or common names are shown in parenthesis next to family of subfamily name. Non-labeled families are parasitoids. Bethylidae, Crabronidae, and Tiphiidae are mostly parasitoids, but some show hunting wasp-like behaviors (marked as partially hunting). Families or subfamilies reviewed in this article are highlighted with bold font.
Figure 1. Composite cladogram showing taxonomic relationship of Aculeata [2,8,9]. Sociality (solitary or social) or common names are shown in parenthesis next to family of subfamily name. Non-labeled families are parasitoids. Bethylidae, Crabronidae, and Tiphiidae are mostly parasitoids, but some show hunting wasp-like behaviors (marked as partially hunting). Families or subfamilies reviewed in this article are highlighted with bold font.
Toxins 08 00032 g001
The venoms of wasps have been considered as a potential source of novel bioactive substances for pharmacological, therapeutic, and agricultural uses [1]. Wasp venoms are known to contain three major groups of molecules, namely, (1) proteins, including enzymes and allergens; (2) small peptides with various functions, including neuro- and antimicrobial activities; and (3) low molecular weight substances, including bioactive amines, amino acids, etc. [1]. However, until now, key components that differentiate between the solitary and social wasp venom have not been accurately identified yet.
Since the venomic properties of parasitoid wasps (Pasasitica) have been well reviewed elsewhere [5], in the present review, we have focused on the venom of the Aculeata hunting wasps, particularly those in the superfamily Vespoidea (Figure 1), with a particular emphasis on the comparative aspects of venom proteins and peptides and their properties between solitary and social wasps.

2. Venom of Hunting Wasps

2.1. General Properties and Origin

Venom is a form of toxin secreted by animals that aims at the rapid immobilization or inactivation of their prey or enemy. Venom components target main critical systems of an organism, such as neuromuscular and hemostatic systems, to achieve the most efficient and rapid immobilization or death of the victim. Since venomous animals prey on many different species, as well as have a defense system against unspecified intruders, they produce various proteins and peptides both with specific molecular targets and those that are active across a wide range of animal species [10].
The remarkable similarities observed in the protein compositions between the venoms from various animal species strongly suggests that a variety of proteins have been commonly and convergently recruited in animal venoms throughout the evolution, and a protein suitable for recruitment has been under structural and/or functional constraints [11,12]. The recruitment and evolution of wasp venom components has satisfied the strict requirements of safety towards the venom-producing wasps and efficiency towards targets, which are largely dependent on individual, populational, and ecological factors [5]. Therefore, it is not surprising that there are many common components in the venoms of different wasp species.
Social wasp venoms (of which the most studied is the venom of the social Vespidae), in general, induce local edema and erythema caused by an increased permeability of the blood vessels in the skin, which is a net effect of active peptides, such as bradykinin-like peptides, mastoparans, and chemotactic peptides. These local reactions of venom peptides produce a prolonged pain that often continues for several hours and itching that can last for days. In addition to these direct effects of wasp stings, immunological reactions caused by venom allergens, such as: phospholipase A (A1 and A2), hyaluronidase; Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis-related proteins (CAP); and serine proteases, have also been frequently observed. Allergic reactions lead to anaphylaxis and, by a large dose of venom, systemic toxic reactions, such as hemolysis, coagulopathy, rhabdomyolysis, acute renal failure, hepatotoxicity, aortic thrombosis, and cerebral infarction [13,14].

2.2. Solitary vs. Social Wasp Venom

The venoms of most solitary wasps are not lethal to the prey. Instead, the venoms induce paralysis and regulation of the prey development and metabolism to maintain the life of the prey while feeding wasp larvae [6]. By contrast, the main function of social wasp venoms appears to be that of defense. Venoms of both solitary and social wasps plays a defensive role by causing a number of symptoms in envenomed predators, including pain, tissue damage, and allergic reactions [6]. Pain is a most common defensive property of venoms, where social wasp venom produces a generally stronger pain than that of solitary wasps. In most cases, pain is accompanied by a potential tissue damage and impairment of normal body functions. In addition, venom contains a number of strong allergens, suggesting that venom allergenicity is likely to have a defensive value. Any wasp producing the venom that induces an acute and systematic allergic reaction (anaphylactic) in a predator can not only immediately stop the predator’s attack, but also traumatize that organism to avoid the wasp [6]. Based on the distinctive venom properties between solitary and social wasps, one can expect considerable differences in the main components from the point of venom function. Since many solitary wasps are specific in selecting prey species, it would be intriguing to investigate the differences in venom composition depending on prey species and the factors that influence the recruitment of different venom substances.

3. Comparative Studies of Solitary vs. Social Wasp Venoms

To characterize the venom of solitary and social hunting wasps, a comparative study of venom gland transcriptome and proteome is mandatory. However, most previous genomic or proteomic analysis has focused on parasitoid wasps. For example, among 44 Hymenoptera genome databases annotated at NCBI [15], only one is that of a hunting wasp: specifically, the European paper wasp, Polistes canadensis. Moreover, only a few studies have dealt with venom gland-specific transcriptomes or proteomes so far, and all of them are limited to the Vespidae family.
Herein, seven expressed sequence tag (EST) libraries and three proteome profiles and the putative functions of the Vespidae wasp venoms were compared and summarized: for solitary wasp venom, Orancistrocerus drewseni [16,17], Eumenes pomiformis [16,18], Rhynchium brunneum [19] (Table 1); for social wasp venom, Vespa tropica [19], V. crabro [20], V. analis [20], V. velutina [21], and Polybia paulista [22] (Table 2). In presenting putative functions of venom components in Table 1 and Table 2, biological functions in venom that have been experimentally tested are marked by underlines. The putative functions of remaining components have been implied on the basis of deduced amino acid sequence homology. Venom peptides of various social wasps in the Vespidae, which are reported individually without transcriptome or proteome analysis, are also reviewed in the next section (Table A1).
A total of 82 and 44 venom proteins (or genes) have been identified from solitary and social wasps, respectively (Table 1 and Table 2) and divided into several categories (e.g., Enzymes, Hemostasis affecting proteins, Muscle-related proteins, etc.). The lower number of venom proteins in solitary wasps does not necessarily indicate that solitary wasp venom components are less diverse that those of social wasps. Rather, this indicates that solitary wasp venoms may have been under-explored and the list in Table 1 is most likely less represented.
Table 1. Venom peptides and proteins from solitary wasps and their putative functions.
Table 1. Venom peptides and proteins from solitary wasps and their putative functions.
Protein/PeptidePutative Function aSpecies bReferences
α-pompilidiotoxinParalysis (Na+ channel blocking)As[23]
β-pompilidiotoxinParalysis (Na+ channel blocking)Bm[23]
Dendrotoxin-likeParalysis (K+ channel blocking)Ep[16,18]
Wasp kininPain productionCa, Cd, Ci, Cm, Mf, Mp[24,25,26]
Mast cell degranulating peptides
Mastoparan-likeAllergic inflammation (Mast cell degranulation), Antimicrobial activityAf, As, Ep, Er, Od1, Od2[16,18,27,28,29,30,31,32]
Chemotactic peptides
Wasp chemotactic peptideInflammatory activity
Antimicrobial activity
Cf, Ep, Od1, Rb[16,18,30,33]
Acetyl-CoA synthaseInvolvement in metabolism of acetateRb[19]
Alcohol dehydrogenaseOxidation of ethanol to acetaldehydeEp[18]
AmidophosphoribosyltransferaseRegulation of cell growthRb[19]
Arginine kinaseParalysisCd, Od1, Ep, Rb[16,19,34]
ATP synthaseATP synthesisOd1, Ep, Rb[17,18]
CarboxylesteraseLipid metabolismRb[19]
Citrate synthaseCatalyzing the citric acid cycleRb[19]
Cytochrome P450 monooxygenaseMetabolism of toxic compoundsOd1, Rb[17,19]
DNA-directed RNA polymeraseSynthesis of mRNA precursorRb[19]
Farnesoic acid O-methyltransferaseRegulation of biosynthetic pathway of juvenile hormoneRb[19]
Glutamate decarboxylaseInvolvement in beta-cell-specific autoimmunityEp[18]
Glyceraldehyde-3-phosphate dehydrogenaseDirect hemolytic factorRb[19]
GlycogeninSynthesis of glycogenRb[19]
HECT E3 ubiquitin ligaseRegulation of cell traffickingEp[18]
HyaluronidaseVenom disseminationEp, Rb[18,19]
Myo inositol monophosphataseRegulation of inositol homeostasisRb[19]
Phospholipase A2Hydolysis of lecithinsEp, Rb[18,19]
Protein tyrosin phosphataseRegulation of cellular processesRb[19]
Serine/threonine protein phosphataseRegulation of biochemical pathwaysRb[19]
Tyrosine 3-monooxygenaseRegulation of dopamine synthesisOd1, Ep[16,18]
Hemostasis affecting proteins
MetalloendopeptidaseInhibition of platelet aggregationOd1, Ep, Rb[18,19]
NeprilysinInhibition of platelet aggregationRb[19]
Serine protease/Chymotrypsin/Thrombin-likeFibrinolytic activity
Kinin releasing activity
Od1, Ep[16]
Muscle-related proteins
ActinRegulation of hemocyte cytoskeleton gene expressionOd1, Ep, Rb[16,19]
AnkyrinAttachment of membrane proteins to membrane cytoskeletonRb[19]
BmkettinDevelopment of flight musclesOd1, Rb[17,19]
CalponinRegulation of myogenesisOd1, Ep, Rb[17,18,19]
Muscle LIM proteinRegulation of myogenesisOd1, Ep, Rb[17,19]
Muscle protein 20 MyomesinRegulation of muscle cotracitonOd1, Ep[17,18]
Anchoring the thick filamentsRb[19]
Myosin heavy chainRegulation of muscle functionsOd1, Ep, Rb[17,18,19]
Myosin light chainModulation of the affinity of myosin for actinOd1, Ep, Rb[17,18,19]
ParamyosinRegulation of thick filament in musclesOd1, Ep, Rb[17,18,19]
TitinAssembly of contractile machinery in muscle cellsOd1, Rb[17,19]
TropomyosinMuscle contractionOd1, Rb[17,19]
TroponinMuscle contractionOd1, Ep, Rb[17,18,19]
TubulinRegulation of hemocyte skeleton genes expressionOd1, Ep, Rb[17,19]
Other proteins/peptides
Chemosensory proteinTransferring metabolism-related small moleculesRb[19]
Cytochrom CProtein wireOd1, Rb[17,19]
Heat shock proteinsPrevention of protein misfoldingOd1, Ep, Rb[16,19]
Insulin-like peptide binding proteinDevelopmental arrest (Inhibition of insulin signaling)Ep[18]
SialinNitrate transporterRb[19]
Sugar transporterMaintenance of glucose homeostasisRb[19]
a The functional categories are either molecular, cellular or biological functions. When biological functions in venom are known, they were underlined; b Wasp species abbreviations: Af, Anterhynchium flavomarginatum; As, Anoplius samariensis; Bm, Batozonellus maculifrons; Ca, Campsomeriella annulata; Cd, Cyphononyx dorsalis; Cf, Cyphononyx fulvognathus; Ci, Colpa interrupta; Cm, Carinoscolia melanosome; Ep, Eumenes pomiformis; Er, Eumenes rubronotatus; Mf, Megascolia flavifrons; Mp, Megacampsomeris prismatica; Od1, Orancistrocerus drewseni; Od2, Oreumenes decorates; Pt, Philanthus Triangulum; Rb, Rhynchium brunneum.
Table 2. Venom peptides and proteins from social wasps and their putative functions.
Table 2. Venom peptides and proteins from social wasps and their putative functions.
Protein/PeptidePutative Function aSpecies bReferences
AvTx-7,8Paralysis (K+ channel blocking)Av[35,36]
Agatoxin-likeParalysis (Ca2+ channel blocking)Vv1[21]
Analgesic polypeptideParalysis (Na+ channel blocking)Vv1[21]
CalsynteninParalysis (Ca2+ channel blocking)Vc[20]
Conophysin-RParalysis (Ca2+ channel blocking)Vv1[21]
Latrotoxin-likeChannel formationVv1[21]
Leucine rich repeat domain-containing proteinParalysis (Involvement in synaptic vescle trafficking)Va2, Vc[20]
Orientotoxin-likeParalysis (Presynaptic effect, lysophospholipase activity)Vo, Vv1[21,37]
Wasp kininPain productionPa, Pc, Pe1, Pe2, Pf, Pi, Pj, Pm1, Pm2, Pp, Pr, Va2, Vc, Vm2, Vt, Vx[20,25,38,39,40,41]
Mast cell degranulating peptides
MastoparanAllergic inflamation (Mast cell degranulation)Ap, Pe2, Pi, Pj, Pm2, Pp, Ps, Rs, Va1, Va2, Vb1, Vb2, Vc, Vd, Vl, Vm1, Vm2, Vo, Vt, Vv1, Vx[19,20,38,42,43,44,45,46,47,48,49,50,51,52,53]
Chemotactic peptides
Wasp chemotactic peptideInflammatory activity
Antimicrobial activity
Ap, Pl, Pm2, Pp, Ps, Va2, Vb2, Vc, Vm1, Vm2, Vo, Vt, Vx[20,38,40,41,45,49,50,52,54]
AcetylcholinesterasePain processing (Hydrolysis of neurotransmitter)Va2, Vc, Vv1[20,21]
AcetyltransferaseSynthesis of acetylcholineVt[19]
Acid phosphataseFemale reproductionVa2, Vc[20]
Acyl-CoA delta-9 desaturaseInsertion of double bond in fatty acidsVt[19]
AMP dependent coa ligaseProduction of fatty acyl-CoA estersVt[19]
Arginine kinaseParalysisVa2, Vc[20]
Argininosuccinate synthaseArginine synthesisVt[19]
ATP-dependent proteaseMediation of protein qualityVt[19]
CarboxylesteraseLipid metabolismVa2, Vc[20]
ChitinaseChitinolysisVa2, Vt[19,20]
Core alpha 1,3-fructosyltransferase AGlycoprotein productionVt[19]
Cytochrome P450 monooxygenaseMetabolism of toxic compoundsVt[20]
Dipeptidyl peptidase IVLiberation of bioactive peptidesVa2, Vb1[20,44]
Esterase FE4SequestrationVc[20]
Fatty acid synthaseBiosynthesis of hormonesVt[19]
Fibrinogenase brevinaseFibrinolysisVv1[21]
Glyceraldehyde-3-phosphate dehydrogenase Glycerol-3-phosphate acyltransferase Glycogenin GTP cyclohydrolase I isoform ADirect hemolytic factorVa2, Vc[20]
Synthesis of triacylglycerolVt[19]
Synthesis of glycogenVa2, Vc[20]
Production of neurotransmitterVt[19]
HyaluronidaseVenom disseminationDm, Pa, Pp, Va2, Vc, Vm1, Vt, Vv3[19,20,55,56,57]
LaccaseOxidation, cuticle sclerotizationVc[20]
Myosin light chain kinaseMuscle contractionVa2, Vc[20]
O-linked n-acetylglucosamine transferaseInsulin signaling reductionVt[19]
Peptidyl-prolyl cis-trans isomeraseImmune mediatorVt[19]
Phospholipase A1Production of lipid mediatorDm, Pa, Va1, Va2, Vc, Vv3[20,57,58]
Phospholipase A2Hydrolysis of lecithinsVa2, Vc, Vv1[20,21]
Phospholipase B1Hydrolysis of lysolecithinsVa2[20]
Phospholipase DInduction of inflammatory responsesVa2, Vc[20]
Phospholipase DDHDSynaptic organizationVa2, Vc[20]
Purine nucleoside phosphorylaseApoptosis of lymphocytesVt[19]
Reverse transcriptaseProduction of high venom yieldVt[19]
Thrombin-like enzymeCoagulation factorVa2, Vv1[20,21]
γ-glutamyl transpeptidaseApoptosis of ovariole cellsVa2, Vc[20]
CAP superfamily
DefensinAntimicrobial activityVa2, Vc[20]
Venom allergen 5Allergenic activityDm, Pa, Pe1, Pf, Va2, Vc, Vf, Vg, Vm1, Vm3, Vp, Vs, Vt, Vv2, Vv3[20,56,57,59,60,61,62]
Hemostasis affecting proteins
Blarina toxinProduction of kininsVv1[21]
Coagulation factor
Platelet aggregation
Platelet aggregation
Factor V activatorCoagulation factorVv1[21]
Nematocyte expressed protein-6
Anticoagulant factor
Inhibition of platelet aggregation
Inhibition of platelet aggregation
Inhibition of platelet aggregation
Va2, Vc, Vv1
Va2, Vc
Ryncolin-3/4Platelet aggregationVv1[21]
Serine protease/Chymotrypsin/Thrombin-likeFibrinolytic activity
Kinin releasing activity
Va2, Vc, Vm1, Vt, Vv1[19,20,21,63]
SnaclecPlatelet aggregationVv1[21]
Vescular endothelial growth factorCoagulation factorVv1[21]
VeficolinPlatelet aggregationVv1[21]
Venom plasminogen activatorFibrinolysisVv1[21]
Venom prothrombin activatorFibrinolysisVv1[21]
Muscle-related proteins
ActinExpression of hemocyte cytoskeleton Va2, Vc[20]
CalponinBinding with actinVa2, Vc[20]
Muscle LIM proteinRegulation of myogenesisVa2, Vc[20]
Myosin heavy chainRegulation of muscle functionsVa2, Vc[20]
ParamyosinRegulation of thick filament in muscleVa2, Vc[20]
TropomyosinMuscle contractionVa2, Vc[20]
TroponinMuscle contractionVa2, Vc[20]
VespinSmooth muscle contractionVm1[64]
Protease inhibitor
Leukocyte elastase inhibitor isoformReduction of tissue damageVc[20]
SerpinImmune suppression (Inhibition of melanization)Va2, Vc[20]
Other proteins/peptides
Anaphase-promoting complex subunit 13Protein degradationVt[19]
Apolipophorin-IIILipid transportVt[19]
Bhlh factor math 6Regulation of developmental processVt[19]
BombolitinAntimicrobial activityVc[20]
CRAL/TRIO domain-containing proteinRegulation of cell growthVt[19]
Cytochrome bTransferring electronsVt[19]
Doublesex isoform 1Sex determination factorVt[19]
Ejaculatory bulb-specific protein 3Odorant binding proteinVa2, Vc[20]
Elongation factor 2Protein synthesisVa2, Vc[20]
Endopeptidase inhibitorInhibition of atrial natriuretic peptidesVt[21]
EndoplasminProtein foldingVa2, Vc[20]
ETR-3 like factor 2Pre-mRNA alternative splicingVt[19]
Gigantoxin-1Hemolytic activityVv1[21]
Growth hormone inducible transmembrane proteinApoptosisVt[19]
GTPase-activating proteinRegulation of G protein signalingVa2[20]
Heat shock proteinsPrevention of protein misfoldingVt[19]
Insulin binding proteinInhibition of insulin signalingVa2, Vc[20]
NADH-ubiquinone oxidoreductase chain 4Involvement in respiratory chainVt[19]
Natterin-4Kininogenase activityVv1[21]
Peptidoglycan-recognition protein 1Antimicrobial activityVt[19]
Phd finger proteinProtein-protein interactionVt[19]
PlancitoxinDNase activityVv1[21]
a The functional categories are either molecular, cellular or biological functions. When biological functions in venom are known, they were underlined; b Wasp spicies abbreviations: Ap, Agelaia pallipes; Av, Agelaia vicina; Dm, Dolichovespula maculate; Pa, Polistes annularis; Pc, Polistes chinensis; Pe1, Polistes exclamans; Pe2, Protopolybia exigua; Pf, Polistes fuscatus; Pi, Parapolybia indica; Pj, Polistes jadwigae; Pl, Paravespula lewisii; Pm1, Paravespula maculifrons; Pm2, Polistes major; Pp, Polybia paulista; Pr, Polistes rothneyi; Ps, Protonectarina sylveirae; Rs, Ropalidia sp.; Va1, Vespa affinis; Va2, Vespa analis; Vb1, Vespa basalis; Vb2, Vespa bicolor; Vc, Vespa crabro; Vd, Vespa ducalis; Vf, Vespa flavopilosa; Vg, Vespula germanica; Vl, Vespula lewisii; Vm1, Vespa magnifica; Vm2, Vespa mandarina; Vm3, Vespula maculifrons; Vo, Vespa orientalis; Vp, Vespula pensylvanica; Vs, Vespula squamosa; Vt, Vespa tropica; Vv1, Vespa velutina; Vv2, Vespula vidua; Vv3, Vespula vulgaris; Vx, Vespa xanthoptera.

3.1. High Throughput Identification of Wasp Venom Components

A recent introduction of the cost-effective RNA sequencing technology in conjunction with bioinformatics has enabled for a more extensive identification of genes encoding venom peptides and proteins from the transcriptome of venom gland, thus allowing for a more comprehensive understanding of venom composition. Initial high throughput analysis of venom gland transcriptome was conducted with parasitoid wasps (reviewed in [5]).
Recently, several papers have reported the transcriptomic analysis of venom gland of social wasps [20,21]. In the transcriptome of V. velutina venom, a variety of hemostasis-impairing toxins and neurotoxins were identified in addition to the genes encoding for well-known venom proteins and peptides. The most abundant hemostasis-impairing toxins consisted of two families based on their mode of action, namely: (1) the hemolytic toxins, including venom plasminogen activator, snaclec, lectoxin-Enh4, and fibrinogenase brevinase, etc.; and (2) the toxins involved in blood coagulation cascade, including factor V activator, oscutarin-C, ryncolin-3/4, veficolin, coagulation factor, thrombin-like enzyme, and venom prothrombin activator [21]. Second in abundance were neurotoxins in V. velutina venom, which were suggested to target either ion channels or synaptic components. Interestingly, genes encoding latorotoxin-orthologs were identified.
In a comparative analysis of the venom gland transcriptomes from two species of social wasps, V. crabro and V. analis, a total of 41 venom-specific genes were commonly identified in both transcriptomes; however, their transcriptional profiles were different [20]. These major venom components were identified and confirmed by mass spectroscopy. Most major venom genes, including prepromastoparan, vespid chemotactic precursor, vespakinin, etc., were more predominantly expressed in V. crabro, whereas some minor venom genes, including muscle LIM protein, troponin, paramyosin, calponin, etc., were more abundantly expressed in V. analis. Taken together, these results suggest that V. crabro venom is more enriched with major venom components and thus is potentially more toxic as compared with V. analis venom. Any gene encoding latrotoxin-like peptide, which was observed in the V. velutina venom transcriptome [21], was not annotated from the transcriptomes of V. crabro and V. analis. Some of the toxins involved in blood coagulation cascade, such as metalloendopeptidase and neprilysin, were identified in the venom gland transcriptomes of V. crabro and V. analis.
In the comparison of bioactivities of mastoparans, a family of major venom peptides, from these two hornets, V. analis mastoparan showed a significantly higher hemolytic activity, suggesting its higher cytotoxic potential as compared to V. crabro mastoparan [65]. In addition, V. analis mastoparan exhibited significantly more potent antimicrobial activities against Escherichia coli and Candida albicans and a significantly higher antitumor activity than V. crabro mastoparan. Such enhanced bioactivities of V. analis mastoparan are likely to be attributable to the additional Lys residue present in the mature peptide, as proposed by the secondary structure prediction [65]. Considering the potential differences in toxicity of each venom component, this finding further implies that, for a better understanding of venom toxicity, it would be necessary to investigate the structural properties of venom components and their quantitative profiles.
To the best of our knowledge, no large-scale transcriptomic analysis of venom gland from solitary wasp has been conducted so far. Instead, the suppression subtractive hybridization (SSH) technique has been employed to enrich the venom gene components of solitary hunting wasps, O. drewseni, E. pomiformis, and R. brunneum [17,18,19,66].
Hyaluronidase and phospholipase A2, which are known to be the main components of wasp venom, were found with high frequencies in the subtractive library of venom gland/sac of O. drewseni [17] along with other enzymes, including zinc-metallopeptidases. The latter are reported to induce hemolysis, hemorrhaging, and inflammation combined with phospholipase A2 and to contribute to prey immobilization and digestion [67,68]. Over 30% of contigs assembled from the library, including one with high abundance, had no BLAST hits, which appeared due to the lack of sufficient venom gland gene database and functional information on many of the venom components. Similarly, a subtractive cDNA library of the venom gland/sac of E. pomiformis was constructed by SSH [18]. Among 102 contigs assembled from the library, 37 contigs were annotated via BLASTx search and manual annotation, of which 8 contigs (337 ESTs) encoded short venom peptides (10 to 16 amino acids) occupying a majority of the library (62%) [18]. Genes encoding a novel dendrotoxin-like peptide containing the Kunitz/BPTI (bovine pancreatic trypsin inhibitor) domain, which is known to be K+ channel blockers, were identified from the library of E. pomiformis venom gland (named EpDTX). In addition to the major components of wasp venom (i.e., hyaluronidase and phospholipase A2), several transcripts encoding metallopeptidases and decarboxylase, which are likely to be involved in the processing and activation of venomous proteins, peptides, amines, and neurotransmitters, were identified [18]. Interestingly, a transcript encoding a putative insulin/insulin-like peptide binding protein (IBP), which was suggested to be involved in growth regulation of their prey, was identified as well.
A proteomic approach in conjunction with the transcriptome analysis has been attempted for the identification of venom components in E. pomiformis and O. drewseni. The venom proteins were identified by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), which was followed by nano electrospray ionization-tandem mass spectrometry (ESI-MS/MS) for protein identification. Over 30 protein bands (2–300 kDa) were detected from the crude venom of each wasp [16]. With the aid of the venom gland/sac-specific cDNA database, a total of 31 and 20 proteins were identified from E. pomiformis and O. drewseni venoms, respectively. The arginine kinase, in both full-length and truncated form, was predominantly found in both wasps’ venoms. However, IBP was found in abundance only in E. pomiformis venom, reflecting its unique behavior of oviposition and provision, which is different from the subsocial O. drewseni [69].
Genes differentially expressed in the venom of social (V. tropica) and solitary (R. brunneum) wasps were investigated by a comparative transcriptome analysis based on SSH [19]. Although no remarkable differences in the distribution of functional categories were observed between the two venom gland/sac cDNA libraries, some groups of genes were found specific to either V. tropica or R. brunneum. When summarized together with the other transcriptomic and proteomic venom studies overviewed above and the proteome profiles of P. paulista [22], it can be concluded that venom allergen 5 and acid phosphatase are specifically present in the social wasp venom, whereas several venom peptides, IBP, and dendrotoxin are more specifically found in the solitary wasp venom gland (Table 1 and Table 2).
To summarize, the combined approach of the venom gland transcriptome analysis, either by full-scale RNA sequencing or SSH-based enriched library sequencing, and the direct analysis of venom components by electrophoresis in conjunction with mass spectrometry has been most widely used to identify venom components, particularly, minor components, of both solitary and social wasps. Annotation of the venom gland/sac cDNA library in conjunction with de novo sequencing of venom peptides followed by transcript structure analysis is a useful approach for confirming the structure of a mature venom peptide and for identifying various novel venom peptides, including those rarely detected by proteomic analysis [66]. While an increasing body of genomic or transcriptomic information on wasp venom toxins has become available to date through the Hymenoptera Genome Database [70], the information on solitary wasp venom is relatively more limited as compared with that on social wasp. This situation highlights the importance of establishing the venom gland transcriptome database of solitary wasps, which is also a prerequisite for the proteomic/peptidomic identification of venom components. The availability of high-throughput technologies for the identification of venom constituents would also facilitate the understanding of the evolution of solitary wasp-prey interactions. However, it should be noted that, for the comparative analysis of venom compositions on the basis of venom gland transcriptome or venom proteome/peptidome, the same criteria should be employed for all analytical procedures (i.e., sample collection, preparation and depth of sequencing or mass spectrometry) to avoid any bias due to the differences in sample and data quality. A guideline for sample preparation can be suggested based on previous studies. In case of venom transcriptome analysis, to obtain 1–10 μg of high quality total RNA for conventional RNA sequencing, dissection of 1–20 venom glands, depending on the size of wasp, from live wasps is recommended [17,18,19,20,21,71]. For venom proteome/peptidome analysis, a sufficient amount of venom can be extracted from 2 to 10 isolated venom sacs (depending on the size of wasp) by centrifugation (1000–10,000 × g for 5~10 min) [16,18,20,72].

3.2. Comparative Aspects of Venom Components between Solitary vs. Social Wasp

Contents of venom components can be directly estimated from their proportion in the proteomic/peptidomic profiles of venom. Alternatively, they can also be indirectly predicted from the proportions of their transcripts in the transcriptome or cDNA library of venom gland. Previous comparisons of the relative contents of venom components suggest that venom peptides (mastoparan-like and chemotactic peptide-like), metalloendopeptidase, hyaluronidase, and arginine kinase are predominantly found in solitary wasps [16,18,19] while mastoparan, vespid chemotactic peptide (VCP), venom allergen 5, serine protease, and hyaluronidase were generally ranked as top five components in social wasps [19,20].
Both solitary and social wasp venoms contain several common components, including hyaluronidase. Hyaluronidase is hydrolase that can hydrolyze the viscous hyaluronic acid polymer, an important constituent of the extracellular matrix of all vertebrates [73]. Hyaluronidase is also commonly found in the venoms of various venomous organisms, including bees and wasps. Due to the degradation of hyaluronic acid in the extracellular matrix, venom hyaluronidase functions as a diffusion factor that facilitates the diffusion of injected venom from the site of sting into circulation, thereby potentiating the action of other venom ingredients [74,75]. Besides, hydrolyzed hyaluronan fragments are known to stimulate inflammation, angiogenesis, and immune response, thereby resulting in a quicker systemic envenomation [76]. Owing to its role in venom spreading, hyaluronidase is common not only in social wasp venoms, but also in solitary wasp venoms as an essential venom ingredient (Table 1 and Table 2). In addition to hyaluronidase, other venom proteins that are commonly found in both wasps include phospholipase A2, metalloendopeptidase, etc., which are also well-known allergens.

3.2.1. Solitary Wasp Venom-Specific Features

Many peptides, which constitute a sizeable portion in solitary wasp venom, are not exactly categorized in the well-defined groups of social wasp venom peptides, such as kinin, mastoparan, or chemotactic peptides. Further detail on individual venom peptides is provided in Section 4. Although it has been expected that more diverse bioactive components with the functions of prey inactivation and physiology manipulation are present in solitary wasps, available studies on venom compositions of solitary wasps are simply too scarce to generalize this notion. Nevertheless, several neurotoxic peptides or proteins appear to be specific to solitary wasps and are involved in prey paralysis.
Non-kinin neurotoxic peptides isolated from Pompilidae solitary wasps [α-pompilidotoxin (α-PMTX) from Anoplius samariensis and β-PMTX from Batozonellus maculifrons] [23,77] are known to affect both vertebrate and invertebrate nervous systems by slowing or blocking sodium channel inactivation [78], thereby paralyzing cockroach prey.
A novel dendrotoxin-like peptide containing the Kunitz/BPTI domain was identified from in A. samariensis (As-fr-19), E. pomiformis (EpDTX), and R. brunneum venoms [16,18,19,79]. Since dendrotoxin is known to block K+ channel, the presence of dendrotoxin-like venom peptides in solitary wasp venoms suggests its involvement in the paralysis of prey.
More extensive research on the components of solitary wasp venom is likely to identify other neuroactive peptides with similar functions. However, it is also worth mentioning that low molecular mass substances functioning as neurotoxin or neuromodulator, such as philanthotoxins found in the Egyptian solitary wasp Philanthus Triangulum venom [80,81,82] and biogenic amines, [e.g., γ-aminobutyric acid (GABA), taurine, and β-alanine] found in the jewel wasp Ampulex compressa venom [83], can play a more decisive role than neuroactive venom peptides in solitary wasps.
In particular, IBP was found to be a major component (22.4% of total venom protein) in the venom of a solitary wasp E. pomiformi [16]. To elucidate biological and molecular functions of EpIBP, EpIBP and its homologous protein of Spodoptera exigua (SeIBP) were in vitro expressed using an E. coli expression system [84]. S. exigua larvae injected with EpIBP exhibited an increased survivorship and a reduced loss of body weight under a starvation condition. Both EpIBP and SeIBP were found to interact with apolipophorin III (apoLp III), implying that EpIBP might control the apoLp III-mediated metabolism, thereby regulating the growth of prey [84]. Similarly, an IBP was also identified in the venom of a parasitoid wasp Nasonia vitripennis and suggested to inhibit the growth of the host [85]. Although IBP was found in the venom gland transcriptomes of V. crabro and V. analis, its transcription level, as judged by the FPKM value, was very low [20]. Considering that the expression level of IBP in a solitary wasp E. pomiformi is much higher [16], IBP in social wasp venom with a negligible level of expression is likely to be non-functional.
Vitellogenin-like protein, which is known to be involved in immune stimulation by enhancing melanin synthesis [86], was identified from both E. pomiformis and O. drewseni venoms, suggesting that they are likely involved in the protection of prey from microbial invasion [16].

3.2.2. Social Wasp Venom-Specific Features

Venom allergen 5 proteins, venom acid phosphatase, and various phospholipases (A1, B1, D, and DDHD) appear to be relatively more specific to social wasp venom (see Table 2). Together with hyaluronidase and acid phosphatase, venom allergen 5 protein is one of the major allergenic Vespid venom proteins [87]. It is reported that venom allergen 5 is a major venom component in social wasps and has been identified in all social wasps examined in the present review (see Table A1). Although the gene encoding venom allergen 5 is found from a solitary wasp R. brunneum [88], it was not identified at all in the venom gland/sac transcriptome and proteome libraries of solitary wasps, including R. brunneum [16,17,18,19], suggesting that it is not common in solitary wasps. Phylogenetic analysis of venom allergen 5 proteins of several Hymenopterans suggests that the gene can date back to the common ancestor of the Ichneumonoidea and the Aculeata, indicating its ancient origin [88]. Since all of the Vespid venom allergen 5 proteins show >57% of sequence identity, the tertiary conformations and allergenic capacities may not significantly differ [20,59]. Thus, a high degree of cross-reactivity in serological testing was observed among the venom allergen 5 proteins of the common group of yellow jackets and among those of the two common North American subgenera of paper wasps [59].
Venom acid phosphatase belongs to the enzyme group which hydrolyzes phosphomonoesters at acidic pH. It has been characterized as a glycoprotein causing histamine release from sensitized human basophils, as well as an acute swelling and flare reaction after intradermal injection into the skin of allergenic patients [89,90,91,92]. Venom acid phosphatase is a high-molecular-weight protein composed of 404–411 amino acid residues in the order Hymenoptera [91,93,94]. Venom acid phosphatase is not common in solitary wasp venoms (Table 1), whereas its gene was found in the venom gland transcriptomes of V. crabro and V. analis (Table 2), suggesting its relatively wider distribution in social wasp venoms and its importance as a major allergen.
Acetylcholine, a neurotransmitter and neuromodulator, is commonly found in social wasp venom and is likely to be involved in pain processing [95]. Acetylcholinesterase, which hydrolyzes the acetylcholine, was specifically identified in social wasps [96], suggesting that it may play a role in the regulation of pain sensation in envenomed vertebrates.
A number of venom proteins tentatively associated with hemostasis have been identified by the venom gland transcriptome analysis of Vespa social wasps (Table 2, [20,21]). A relatively fewer numbers of hemostasis-related proteins have been identified from solitary wasps (Table 1), suggesting that this group of proteins are likely to be associated with social defense by disrupting hemostasis of vertebrate predators.

4. Venom Peptides

Among a variety of venom components, peptides with a molecular weight range of 1.4–7 kDa are predominant in wasp venoms, comprising up to 70% of the dried venoms [14,18,19,20,66]. In addition to neurotoxic peptides including wasp kinins, a series of amphipathic α-helical peptides (mastoparans and chemotactic peptides) are also major peptidergic components. These venom peptides commonly exist in both solitary and social wasp venoms. However, no kinins have been identified yet in Vespidae solitary wasps. Only three chemotactic peptide-like peptides have been reported in Vespidae solitary wasps so far, implying that kinin-like peptides are not likely a major component in Vespidae solitary wasp venoms (Table A1).
Kinins, mastoparans, and chemotactic peptides share a common secondary structure: an N-terminal signal sequence, a prosequence, a mature peptide, and/or an appendix G or GKK at the C-terminus. They are post-translationally processed via the sequential liberation of dipeptides (A/P-X-A/P-X) in the prosequence by dipeptidyl peptidase IV (DPP-IV) [44,97]. Additionally, some of mastoparans and chemotactic peptides are further processed at C-terminal G or GKK residues via the C-terminal amidation catalyzed by peptidylglycine α-hydroxylating monooxygenase and peptidyl-α-hydroxyglycine α-amidating lysase [98,99]. Although many venom peptides pass through a similar posttranslational processing, the matured peptides have distinguishable structures and bioactivities. Moreover, several venom peptides matured via the same processing are not even categorized into kinin, mastoparan, or chemotactic peptides in solitary wasps (e.g., 6 venom peptides from O. drewseni and E. pomiformis in “Uncategorized Peptides” in Table A1). Since peptides are major components of both solitary and social wasp venoms, their kinds, properties, and putative functions are reviewed in detail in this section.

4.1. Neurotoxic Peptides

Neurotoxic peptides modulating ion channel and receptor functions have been described in wasp venoms. The first neurotoxin component that was isolated from wasp venom was a nicotinic acetylcholine receptor (nAChR) inhibitor, kinin. In 1954, the first wasp kinin was isolated from a social wasp, Vespa vulgaris [100]. Afterwards, many kinins of the Vespoidea wasp venoms were found to be responsible for the pain and paralysis after a wasp sting [24,101]. Until now, most of the neurotoxic peptides of hunting wasps are kinins. Wasp kinins will be discussed further in Section 4.2.
There are 2 non-kinin neurotoxic peptides isolated from Pompilidae solitary wasps: α-PMTX from A. samariensis and β-PMTX from B. maculifrons [23,77]. PMTXs, 13-amino acid venom peptides, affect both vertebrate and invertebrate nervous systems by slowing or blocking sodium channel inactivation [78]. α-PMTX greatly potentiates synaptic transmission of lobster leg neuromuscular junction by acting primarily on the presynaptic membrane [77]. Interestingly, β-PMTX, in which the lysine at 12 position of α-PMTX was replaced with arginine, is 5 times more potent than α-PMTX [23].
Recently, novel venom peptides, AvTx-7 and AvTx-8, were also reported as neurotoxins of the social wasp Agelaia vicina [35,36]. Although their primary structures have not been elucidated so far, they seem to be new types of venom peptides, different from kinins as judged by their distinct neural activity. AvTx-7 stimulates glutamate release through K+ channel and AvTx-8 inhibits GABAergic neurotransmission, whereas wasp kinins block nAChR.

4.2. Kinins

Bradykinin was first reported in 1949 as a mammalian blood serum substance that triggers a slow contraction of the guinea-pig ileum [102]. This nonapeptide acts on smooth muscles with contractions or relaxations. In the neuronal cells of vertebrates, bradykinin evokes a release of neuropeptides (galanin, neuropeptide Y, and vasoactive intestinal peptide) and catecholamines (dopamine, norepinephrine, and epinephrine) by depolarizing nerve terminals [25,103].
Bradykinin-like peptide was found in wasp venoms as the first neurotoxic and pain-producing peptide [100]. It irreversibly blocks the synaptic transmission of nAChR in the insect central nervous system (CNS) [104,105]. While wasp kinins have remarkable sequence similarities to the main structure of mammalian bradykinin [-PPGF(T/S)P(F/L)-], most of them are longer than bradykinin or differ at position 3 or 6, where proline is replaced by hydroxyproline or serine is replaced by threonine (Thr6-bradykinin), which has a single extra hydroxyl or methyl group, respectively. By the single amino acid substitution, Thr6-bradykinin displayed 3-fold higher anti-nociceptive effects on the rat CNS and remained active longer than bradykinin [106]. Considering their action on nAChR, bradykinins in solitary wasp venoms may play a crucial role in paralyzing prey during hunting [24].
Almost all social wasp venoms may have kinin or kinin-like activities, while, among solitary wasps, Cyphononyx dorsalis (Pompilidae) and several Scoliidae wasps have Thr6-bradykinin in their venom, and bradykinin was found only in the Megacampsomeris prismatica (Scoliidae) venom [24,107]. Since one of major pharmacological effects of kinins is pain sensation in vertebrates [108], the ubiquitous distribution of kinins in social wasp venoms suggests that kinins may function as a major defense and alarm device by generating pain in the envenomed vertebrate predators. The presence of kinins in the venom of Vespidae and Scoliidae, as well as that of Formicidae (ants), and no kinin-like activities in bees (Apidae) and bee-related solitary wasps (Crabronidae and Sphecidae) was supposed to support the suggestion that these three families are associated by synapomorphies [2,25]. Later on, however, kinin-like activity was also found in Ampulicidae (A. compressa) that is closely located to Apidae [109], and no kinins have been isolated from solitary wasps in Vespidae so far. Thus, the relationship between the venom kinins and evolution remains obscure, requiring a more extensive identification and characterization of Hymenopteran venom kinins.

4.3. Mastoparans

The most abundant peptide component of hunting wasp venoms, both in solitary and social wasps, is mastoparan. Of note, however, mastoparans have been thus far isolated only in Vespidae (both social and solitary), not in other solitary hunting wasp families. Mastoparans (mostly tetradecapeptides) act on mast cells to liberate granules and release histamine (mast cell degranulation, MCD), resulting in inflammatory response [110]. Their structural properties, net positive charge, and amphipathic α-helical structure, in which all side chains of the hydrophobic amino acids are located on one side of the axis, and those of the basic or the hydrophilic amino acid residues are on the opposite side, allow them to attach to biomembranes and form pores via barrel-stave, carpet, or toroidal-pore mechanisms, resulting in an increase of cell membrane permeability [111]. Mastoparans are often highly active against the cell membranes of bacteria, fungi, and erythrocytes, as well as mast cells, resulting in antimicrobial, hemolytic, and MCD activities. Meanwhile, MCD by mastoparan may occur also through the exocytosis of granules, triggered by mastoparan modulating G-protein activity without receptor interaction [112]. The net effect of MCD depends on the cell types: the secretion of histamine from mast cells, serotonin from the platelets, catecholamines from chromaffin cells, prolactin from the anterior pituitary, and even insulin from pancreatic β-cells [51,110,113]. Cell lytic activity also varies depending on the cell types. Generally, antimicrobial activity of mastoparans is higher against fungi than Gram-negative bacteria, E. coli [45,114]. In addition, probably due to the cell lytic activity against insect cells, antimicrobial mastoparans also caused feeding disorder in caterpillars, although they are not active against human erythrocytes [114].
Cell lytic activity of mastoparans also leads to mitochondrial permeability transition that affects cell viability and triggers tumor cell cytotoxicity (reviewed in [115]). Besides MCD and cell lytic activity, mastoparans also stimulate phospholipases A, C and D, mobilization of Ca2+ from mitochondria and sarcoplasmic reticulum, and necrosis and/or apoptosis [115,116]. A variety of biological functions of mastoparans have attracted attention to them as components for potential therapeutic and biotechnological applications in biomedicine (reviewed in [115,117]). Due to the lack of cell specificity, however, mastoparans could not be used as they are. That is, they would damage not only tumor cells, but would also negatively affect healthy cells. Accordingly, researchers are developing a delivery system for venom peptides targeting tumor cells and a selective release system inside tumor cells that would make venom peptides accumulate in a specific and controlled manner [118].

4.4. Chemotactic Peptides

The second major peptide group in hunting wasp venom is chemotactic peptides. Similarly to mastoparans, venom chemotactic peptides have also been isolated only from social and solitary wasps in Vespidae, not from other solitary wasp families. Like mastoparans, venom chemotactic peptides are generally tridecapeptides with an amphipathic, α-helical, linear, cationic, and C-terminal amidated secondary structure. Their primary activity is described as inducing cellular chemotactic response in polymorphonuclear leukocytes and macrophages [119] and, due to the structural homology, chemotactic peptides often reveal mastoparan-like MCD, antimicrobial, and hemolytic activities. Chemotactic activity results in a mild edema, accompanied by an inflammatory exudate around the stinging site, where polymorphonuclear leukocytes are mainly concentrated. In other words, chemotactic peptides do not directly trigger pain, but enhance the inflammatory response by wasp stings [1]; therefore, they are likely to be involved in defense. Their widespread distribution in most social wasp venoms supports this prediction.
Although chemotactic peptides are a major venom component, only three of them have been reported in the venom of solitary hunting wasps: Orancis-protonectin (OdVP2) [30,66], EpVP6 [18], and the one found in R. brunneum (named RbVP1 hereafter) [19]. These solitary wasp venom peptides were categorized into chemotactic peptides based on the amino acid sequence homology with the previously known peptides, without a chemotaxis analysis. Thus, they indeed should be further evaluated to be referred to chemotactic peptides.
There is no known conserved main structure for recognition of venom chemotactic peptides. In Table A1, venom chemotactic peptides reported in solitary and social hunting wasps are summarized and compared, revealing representative motives XX(G/R)XX, XX(G/A/S/R/K/T)(G/T/K/S)XX or, sometimes, an overlapped form of the two motives, where X is a hydrophobic amino acid, most frequently, Ile or Leu. While only some mastoparanshave these motives, all chemotactic peptides have them. In addition, chemotactic peptides possess no or only one Lys residue, rarely 2 (RbVP1 and HR2), while most of mastoparans have 2 or 3 Lys residues. Mastoparans with 3 Lys residues generally have a single Lys (-K-) and separately double Lys residues (-KK-). These characteristics were inferred from the sequences collected during the preparation of the present manuscript, thereby the two motives suggested above are not fully confirmed yet.

4.5. Other Venom Peptides

Many peptides in solitary wasp venom are not exactly categorized in kinin, mastoparan, or chemotactic peptides. Most of them are not functionally analyzed.
Amphipathic linear cationic α-helical peptides anoplin and decoralin, found in a Pompilidae wasp A. samariensis and an Eumeninae wasp Oreumenes decoratus, respectively, commonly have MCD and antimicrobial activities [27,28,120]. Anoplin has hemolytic activity as well [121].
Non-helical coil venom peptides OdVP4, EpVP3, EpVP3S, EpVP4a, EpVP4b, and EpVP5 of Eumeninae wasps have neither antimicrobial and hemolytic, nor insect cell lytic activities [18,66,114], which implies that those peptides might have novel properties other than cell lytic activity.
Bioactivities of As-peptide126, Cd-125 and Cd-146 [107], isolated from Pompilidae wasps, have not been evaluated so far. Another A. samariensis venom peptide As-fr-19, as well as its homologue EpDTX of E. pomiformis, has a sequence similarity to potassium or calcium channel blocker, dendrotoxins from snakes, cone snails, and sea anemones [18,79]. The precise biochemical functions of As-fr-19 and EpDTX have not been clarified so far, but they are likely to function as neurotoxins.
Vespin of Vespa magnifica, a 44 amino-acid peptide, exerts contractile effects on isolated guinea pig ileum smooth muscle by interacting with bradykinin receptors [64]. However, vespin does not share the conserved motif of kinins [-PPGF(T/S)P(F/L)-], suggesting that vespin is a novel kind of venom peptide with kinin-like activity.
Recently, genes encoding putative neurotoxic peptides (i.e., agatoxin-like, conophysin-R-like, latrotoxin-like and orientotoxin-like) have been identified from the venom transcriptome of V. velutina, though their transcription levels were very low [21]. Neurotoxic effects of these tentative venom peptides remain to be addressed in further research.

5. Useful Wasp Venom Components for Pharmacological, Medical, and Agricultural Applications

Considering the huge diversity of wasp venom components, wasp venoms can be employed as a rich source of novel bioactive substances for pharmacological, therapeutic, and agricultural applications [1]. Some venom proteins and peptides have been exploited as candidates for the discovery of novel therapeutic agents. Furthermore, studies on social wasp venoms have provided crucial information on the main allergenic molecules that are responsible for the hypersensitivity reaction in humans and enabled for the development of immunotherapy for preventing venom-induced anaphylaxis [122,123]. Similarly to the venom of parasitoid wasps, venoms of solitary hunting wasps are also known to contain various substances that can manipulate the physiology of prey [16,84,124]. Such regulatory molecules produced by wasps would serve as innovative leads for developing novel, environmentally safe insect control agents [124].

5.1. Antimicrobial Agents

Antimicrobial peptides (AMPs), which are relatively small (<10 kDa), cationic, and amphipathic peptides, are a basic humoral immune component of most organisms, including wasps, against invading microbial pathogens [125,126]. These AMPs exhibit a broad-spectrum antimicrobial activity against various microorganisms, including Gram-positive and Gram-negative bacteria, protozoa, yeast, and fungi [127]. Over the last several decades, a number of AMPs, mostly belonging to the groups of mastoparans, VCPs, and kinins, have been isolated from a wide variety of wasp species [50]. Most AMPs with the origin of wasp venom belong to the peptides forming alpha-helical structures, or coils rich in cysteine residues [111,114] and are suggested to act by perforating the plasma membrane, thus resulting in the cell lysis and death [111].
Mastoparan or mastoparan-like peptides are the alpha-helical peptides and have been identified in a wide range of wasps, including both solitary and social wasps [16,18,19,20,27,28,29,30,31,32,38,42,43,44,45,46,47,48,49,50,51,52,53]. The AMP from the Brazilian wasp P. paulista venom (MP1) has a broad-spectrum antibiotic activity against Gram-negative and Gram-positive bacteria without showing apparent hemolytic and cytotoxic activities [42]. The applicability of mastoparans for therapeutic and biotechnological use has been also reviewed elsewhere [115].
Three venom peptides (OdVP1, OdVP2 and OdVP3) isolated from the venom of the solitary wasp O. drewseni showed the typical features of amidated C-termini proteins and had a high content of hydrophobic and positively charged amino acids, resembling the amphipathic α-helical secondary structure of mastoparans [66]. Despite the distinctive sequences context in mature peptide, the overall transcript structure of the OdVPs showed a high similarity to that of Vespa basalis mastoparan-B by containing a signal sequence, a prosequence, a mature peptide, and a C-terminal glycine [66]. The OdVPs exhibited strong activities against fungi, but weak antibacterial activities. OdVP2L, having additional Glu–Pro residues, showed a high antifungal activity against the gray mold Botrytis cinerea, but did not show antimicrobial activity against bacteria or Gram-positive yeast [66]. Venom peptides of a-helical structure from a solitary wasp E. pomiformis (EpVP1, EpVP2a, EpVP2b, and EpVP6) also exhibited varying degrees of anti-microbial activities against Gram-negative E. coli, Gram-positive Staphylococcus aureus, Gram-positive yeast C. albicans, and the gray mold B. cinerea [114].
Since microbial infection mediated by biofilms has been a major problem in the use of implantable devices, several approaches, including the covalent immobilization of AMPs, have been attempted to tackle this problem [128]. To this end, the immobilization of MP1, a broad-spectrum AMP from a social wasp P. paulista venom, onto silicon surfaces has been attempted via the “allyl glycidyl ether brush”-based polymerization chemistry [129]. The antibacterial activity of the MP1-immobilized surfaces was retained after 3 days of incubation in artificial urine without causing any significant cytotoxicity against human red blood cells, suggesting the stability and safety of the AMP coating in physiological environments [129]. Based on this finding, a general approach to exploit and immobilize other AMPs as novel surface-sterilizing agents can be attempted.

5.2. Antitumor Agents

Mitoparan, a synthetic mastoparan analog, can form pores in the cancer cell plasma membrane and eventually lead to its death either by necrosis or by triggering apoptosis [130,131]. Due to their non-specific cytolytic activity and instability when injected in blood, however, the use of cytosolic peptides, such as mitoparan, is limited [118]. To overcome this limitation, Moreno et al., (2014) have devised a pro-cytotoxic system based on mitoparan conjugated to poly(l-glutamic acid) PGA polymer through specific cleavage sequences that are cleaved by overexpressed tumor proteases, such as the metalloproteinase-2 or cathepsin B, in which the conjugated mitoparan becomes active only when it reaches cancer cells, then is cleaved and released by the tumor proteases [118].
The MP1 AMP, a mastoparan-like pore-forming peptide, has been determined to have highly selective antitumor activities against several types of cancer cells, including bladder and prostate cancer cells [132] and multidrug-resistant leukemic cells [133]. Recently, the highly specific antitumor activity of MP1 was determined to be due to its selective affinity to phosphatidylserine (PS) and phosphatidylethanolamine (PE), thereby enhancing the MP1-driven poration of cancer cell membrane, in which the outer lipid bilayer has an enriched PS and PE composition [134]. When combined with other anticancer drugs, the selectivity of MP1 peptide to disturb the cancer cell membrane may provide synergistic potentials, which can dramatically improve the therapeutic efficacy [134]. The mastoparans from social wasps V. crabro and V. analis also exhibited antitumor activities against ovarian tumor cells, with V. analis mastoparan showing a greater antitumor activity [65]. Taken together, mastoparan-like peptides from wasps can serve as good candidates for lead compounds of novel anticancer drugs [134].

5.3. Venom Allergy Diagnosis and Immunotherapy

Hymenoptera venom allergy (HVA) is an anaphylactic reaction of human to stings of social Hymenopteran insects, including honey bees, yellow jackets, hornets, bumble bees, and paper wasps [122]. A small but significant portion (0.3%–3.4%) of general human population is known to show systemic allergic reactions to Hymenoptera stings [122]. While whole venoms have been usually used for both diagnosis and immunotherapy, their diagnostic precision, when based on whole venom preparations, has been often impaired by immunoglobulin E (IgE) cross-reactivity between different venoms, which might be due to highly conserved venom allergens present in venom of different families or due to the presence of common cross-reactive carbohydrate determinants on venom allergens [122,135]. Nevertheless, the information on single venom allergens for diagnostic and therapeutic purposes has been limited, impeding an in-depth understanding of molecular basis underlying HVA. Recent employment of omics technologies for venom study has enabled a rapid discovery of novel venom components of medical importance and, thus allowed for a better molecular understanding of the entire “venome” as a system of unique and characteristic components [122]. Recombinant allergens, such as phospholipase A1, hyaluronidase, and venom allergen 5, have been generated from four important genera in Vespidae (i.e., Vespula, Dolichovespula, Vespa, and Polistes) and used for diagnosis (reviewed in [136]). When the IgE-binding capacity of recombinant and purified natural venom allergens was compared, recombinant allergens exhibited higher specific responses without cross-reactivity and false positive results, indicating that they are better than highly purified natural preparations in terms of the clinical relevance of an individual allergen [73,137]. The potential of recombinant allergens for diagnostic and therapeutic applications has been well reviewed by Muller (2002) [136]. The use of cocktails with recombinant allergens for diagnosis can significantly increase the specificity of conventional diagnostic tests, such as immediate-type skin tests and the assays for serum-specific IgE antibodies [136]. The hypoallergenic mutants or modified variants of major venom allergens or the T-cell epitope peptides generated by recombinant technologies can be used as vaccines for immunotherapy to treat HVA [57,136].

5.4. Biopesticides

Manipulation of host by parasitoid wasp venom can be achieved via a variety of means, such as transient paralysis, immune suppression, endocrine dysfunction, metabolic alteration, and developmental arrest (reviewed in [124]). Several peptide/protein neurotoxins, including AvTx, pompilidotoxin, agatoxin-like, latrotoxin-like, orientotoxin-like, dendrotoxin-like peptides, among others, have been identified in solitary and social wasp venoms, of which those from solitary wasps (i.e., pompilidotoxin and dendrotoxin-like peptide) are known to be involved in prey paralysis (Table 1 and Table 2; [16,18,23,77,78,138,139]). However, only one venom component that can regulate prey physiology has been identified and characterized in solitary wasps [16,18,51,84]. Nevertheless, given that solitary hunting wasps are also in need of the long-term metabolic alteration and developmental arrest of prey to provide fresh provisions to their progeny, a more versatile array of physiology-manipulating components is likely to be present in the venom of solitary wasps. Once these protein/peptide components with insecticidal or growth-regulating activity are identified, they can be exploited as alternative insect control agents, provided proper delivery protocols are established [140]. A spider venom neurotoxin (Segestria florentina toxin 1, SFI1) fused to the snowdrop lectin (Galanthus nivalis agglutinin, GNA) exhibited insecticidal activity against two homopteran sucking pests, the peach-potato aphid Myzus persicae and the rice brown planthopper Nilaparvata lugens [141], where the fusion protein gene can be employed for developing sucking pest-resistant transgenic crops. More recently, the ω-hexatoxin-Hv1a peptide (Hv1a), a neurotoxin from the Australian funnel web spider Hadronyche versuta acting on voltage-sensitive calcium channels, was fused to the carrier protein GNA to make Hv1a traverse the insect gut epithelium and access the central nervous system, thereby enhancing its oral toxicity [142,143]. In addition, recombinant baculoviruses expressing insect-selective toxins, hormones, or enzymes could enhance their insecticidal properties [144]. Once such neurotoxins or host/prey-regulatory molecules are identified and characterized from wasp venoms, similar biotechnical approaches can be attempted. Therefore, further research is needed for searching and characterizing wasp venom components with insecticidal and growth-regulating potential.

6. Concluding Remarks

Most studies on Hymenopteran venoms have been mainly focused on bees, parasitoid wasps, and social wasps. Possibly due to the limitation in sampling and venom collection, only very few previous studies have been conducted to identify and characterize the constituents of solitary wasp venoms. However, in view of diversity, ecology, and prey-specific behavior of solitary wasps, their venoms are still rich sources of novel bioactive substances. Recent introduction of cost-effective and high-throughput deep-sequencing technologies has enabled a rapid identification of genes encoding various venom peptides/proteins from venom gland transcriptomes. In addition, availability of highly sensitive mass spectrometry techniques allows for a more efficient proteomic/peptidomic analysis of a limited amount of solitary wasp venoms. A systematic and comparative analysis of venoms from solitary vs. social wasps would provide further insights into the venom evolution and phylogeny. Accumulation of functional data on bioactivity of various venom components would facilitate the application of wasp venoms for pharmacological, medical, and agricultural purposes.


This study was supported by a grant from the National Institute of Biological Resources (NIBR), funded by the Ministry of Environment (MOE), Republic of Korea (NIBR No. 2015-12-205). KAY was supported in part by the Brain Korea 21 program.

Author Contributions

S.H.L., J.H.B., and K.A.Y. wrote this manuscript; S.H.L prepared the outline and revised the manuscript; J.H.B participated in venom peptide information searching and K.A.Y searched venom protein information; All authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Appendix A

Table A1. Venom peptides of hunting wasps.
Table A1. Venom peptides of hunting wasps.
SocialityNameSequenceLength (a.a)SpeciesReferences
Solitaryα-PMTXRIKIGLFQDLSKL13Anoplius samariensis[23]
β-PMTXRIKIGLFQDLSRL13Batozonellus maculifrons[23]
SocialAvTx-71210 Da (α-PMTX 1530 Da)-Agelaia vicina[36]
AvTx-81567 Da-Agelaia vicina[35]
SolitaryBradykinin (BK)RPPGFSPFR9mammal-
MegascoliakininRPPGFTPFRKA11Megascolia flavifrons[145]
BradykininRPPGFSPFR9Megacampsomeris prismatica[24]
Thr6-BKRPPGFTPFR9Megacampsomeris prismatica, Campsomeriella annulata annulata, Carinoscolia melanosoma fascinate, Cyphononyx dorsalis, Megascolia flavifrons, Colpa interrupta[24,105,145]
SocialRA-Thr6-BradykininRARPPGFTPFR11Polybia paulista[40]
RA-Thr6-Bradykinin-DTRARPPGFTPFRDT13Polybia paulista[40]
Vespakinin-MGRPHypGFSPFRID14Vespa mandarinia[146]
Vespakinin-XARPPGFSPFRIV12Vespa xanthoptera[147]
Vespakinin-AGRPPGFSPFRVI12Vespa analis[148]
Vespakinin-AP **ELPPGFTPFRII12Vespa analis parallela[20]
Vespakinin-TGRPHypGFSPFRVI12Vespa tropica[101]
Vespakinin-CKLPPGFTPFRII12Vespa crabro flavogasciata[20]
VespulakininTAT(carbhy)T(carbhy)RRRGRPPGFSPFR17(Para)Vespula maculifrons[149]
Vespulakinin-LTAR(NAcGal-Gal)TKRRGRPPGFSPFR17Vespula lewisii[101]
Polisteskinin 3PyrTNKKKLRGRPPGFSPFR18Polistes exclamans, Polistes annularis, Polistes fuscramatus[25]
Polisteskinin-RARRPPGFTPFR11Polistes rothneyi[25]
Polisteskinin-JRRRPPGFT(S)PFR11Polistes jadwigae[101]
Polisteskinin-CSKRPPGFSPFR11Polistes chnensis[101]
PMM1KRRPPGFTPFR11Polistes major major[38]
Protopolybiakinin-IDKNKKPIRVGGRRPPGFTR19Protopolybia exigua[39]
Protopolybiakinin-IIDKNKKPIWMAGFPGFTPIR19Protopolybia exigua[39]
Mastoparan-like Peptides
SolitaryEMP-AFINLLKIAKGIIKSL-NH214Anterhynchium flavormarginatum micado[150]
EumenitinLNLKGIFKKVASLLT15Eumenes rubronotatus[29]
EMP-OD (OdVP1)GRILSFIKGLAEHL-NH214Orancistrocerus drewseni[30,66,114]
OdVP3 aKDLHTVVSAILQAL-NH214Orancistrocerus drewseni[66,114]
EpVP1 aINLKGLIKKVASLLT15Eumenes pomiformis[18,114]
EpVP2a aFDLLGLVKKVASAL-NH214Eumenes pomiformis[18,114]
EpVP2b aFDLLGLVKSVVSAL-NH214Eumenes pomiformis[18,114]
SocialMastoparan (MP)INLKALAALAKKIL-NH214Vespula lewisii[110]
Mastoparan-XINWKGIAAMAKKLL-NH214Vespa xanthoptera[46]
Mastoparan-AIKWKAILDAVKKVL(I)-NH214Vespa analis[20,30]
Mastoparan-BLKLKSIVSWAKKVL-NH214Vespa basalis[30]
Mastoparan-CINW(L)KALLAVAKKIL-NH214Vespa crabro[20,30]
Mastoparan-IIINLKALAALVKKVL-NH214Vespa orientalis[30]
HR1INLKAIAALVKKVL-NH214Vespa orientalis[37]
Mastoparan-T1 *INLKVFAALVKKFL-NH214Vespa tropica[19]
Mastoparan-T2 *INLKVFAALVKKLL-NH214Vespa tropica[19]
Mastoparan-T3 *INLRGFAALVKKFL-NH214Vespa tropica[19]
Mastoparan-T4 *INLFGFAALVKKFL-NH214Vespa tropica[19]
protopolybia-MP IINWLKLGKKVSAIL-NH214Protopolybia exigua[46]
protopolybia-MP IIINWKAIIEAAKQAL-NH214Protopolybia exigua[46]
protopolybia-MP IIIINWLKLGKAVIDAL-NH214Protopolybia exigua[46]
P-8INWKALLDAAKKVL-NH214Protonectarina sylveirae[151]
polybia-MP IIDWKKLLDAAKQIL-NH214Polybia paulista[43]
polybia-MP IIINWLKLGKMVIDAL-NH214Polybia paulista[42]
polybia-MP IIIIDWLKLGKMVMDVL-NH214Polybia paulista[42]
polybia-MP IVIDWLKLRVISVIDL-NH214Polybia paulista[40]
polybia-MP VINWHDIAIKNIDAL-NH214Polybia paulista[40]
polybia-MP VIIDWLKLGKMVM11Polybia paulista[40]
parapolybia-MPINWKKMAATALKMI-NH214Parapolybia indica[46]
parapolybia-MPINWAKLGKLALEVI-NH214Parapolybia indica[30]
polistes-MPVDWKKIGQHILSVL-NH214Polistes jadwigae[46]
PMM2INTKKIASIGKEVLKAL-NH217Polistes major major[38]
Agelaia MP-IINWLKLGKAIIDAL-NH214Agelaia pallipes pallipes[52]
Chemotactic Peptides
SolitaryOdVP2 (Orancis-protonectin)ILGIITSLLKSL-NH212Orancistrocerus drewseni[30,66,114]
EpVP6 bFGPVIGLLSGILKSLL16Eumenes pomiformis[18,114]
RbVP1 *,bFLGGLIKGLVKAL-NH213Rhynchium brunneum[19]
SocialProtonectinILGTILGLLKGL-NH212Protonectarina sylveirae, Agelaia pallipes pallipes[52]
Protonectin(1-6)ILGTIL-NH26Agelaia pallipes pallipes[152]
Paulista-CP (polybia-CP)ILGTILGLLKSL-NH212Polybia paulista[43]
Polybia-CP 2ILGTILGKIL10Polybia paulista[40]
Polybia-CP 3ILGTILGTFKSL-NH212Polybia paulista[40]
CrabrolinFLPLILRKIVTAL-NH213Vespa crabro[153]
Ves-CP-TFLPILGKILGGLL-NH213Vespa tropicaP17231, [19]
Ves-CP-T2 *FLPIIGKLLSGLL-NH213Vespa tropica[19]
Ves-CP-MFLPIIGKLLSGLL-NH213Vespa mandarinaP17232
Ves-CP-AFLPMIAKLLGGLL-NH213Vespa analis, Vespa analis parallelaP17233, [20]
Ves-CP-XFLPIIAKLLGGLL-NH213Vespa xanthopteraP17234
Ves-CP-LFLPIIAKLVSGLL-NH213Vespula lewisiP17235
VCP-5eFLPIIAKLLGGLL-NH213Vespa magnifica[45]
VCP-5fFLPIPRPILLGLL-NH213Vespa magnifica[45]
VCP-5gFLIIRRPIVLGLL-NH213Vespa magnifica[45]
VCP-5hFLPIIGKLLSGLL-NH213Vespa magnifica[45]
HP-1LFRLIAKTLGSLM13Vespa basalis[154]
HP-2LFRLLANTLGKIL13Vespa basalis[154]
HP-3IFGLLAKTLGNLF13Vespa basalis[154]
HR2FLPLILGKLVKGLL-NH214Vespa orientalis[37]
PMM3FLSALLGMLKNL-NH212Polistes major major[38]
Uncategorized Peptides
SolitaryAnoplinGLLKRIKTLL-NH210Anoplius samariensis[27]
DecoralinSLLSLIRKLIT-NH211Oreumenes decoratus[28]
OdVP4LDPKVVQSLL-NH210Orancistrocerus drewseni[66,114]
EpVP3AINPKSVQSLL-NH211Eumenes pomiformis[18,114]
EpVP3SINPKSVQSLL-NH210Eumenes pomiformis[18,114]
EpVP4aLSPAVMASLA-NH210Eumenes pomiformis[18,114]
EpVP4bLSPAAMASLA-NH210Eumenes pomiformis[18,114]
EpVP5VHVPPICSHRECRK14Eumenes pomiformis[18,114]
As-peptide126QDPPVVKMK-NH29Anoplius samariensisBAF65255
Cd-125DTARLKWH8Cyphononyx dorsalis[107]
Cd-146SETGNTVTVKGFSPLR16Cyphononyx dorsalis[107]
* No name in the reference. Named in this review. ** Named the same with a previously known, different peptide. Renamed in this review. a Categorized as mastoparan-like peptides based on the sequence similarity with the previously reported venom peptides, without a mast cell degranulation activity test. b Categorized as chemotactic peptide-like peptides based on the sequence similarity with the previously reported venom peptides, without a chemotactic activity test.


  1. Piek, T. Venoms of the Hymenoptera: Biochemical, Pharmacological, and Behavioural Aspects; Academic Press: London, UK, 1986; p. 570. [Google Scholar]
  2. Brothers, D.J. Phylogeny and evolution of wasps, ants and bees (Hymenoptera, Chrysidoidea, Vespoidea and Apoidea). Zool. Scr. 1999, 28, 233–249. [Google Scholar] [CrossRef]
  3. Dowton, M.; Austin, A.D. Simultaneous analysis of 16S, 28S, COI and morphology in the Hymenoptera: Apocrita—Evolutionary transitions among parasitic wasps. Biol. J. Linn. Soc. 2001, 74, 87–111. [Google Scholar]
  4. O’Neill, K.M. Solitary Wasps: Behavior and Natural History; Comstock Pub. Associates: Ithaca, NY, USA, 2001; p. 406. [Google Scholar]
  5. Moreau, S.J.M.; Asgari, S. Venom proteins from parasitoid wasps and their biological functions. Toxins 2015, 7, 2385–2412. [Google Scholar] [CrossRef] [PubMed]
  6. Evans, D.L.; Schmidt, J.O. Insect Defenses: Adaptive Mechanisms and Strategies of Prey And Predators; State University of New York Press: Albany, NY, USA, 1990; p. 482. [Google Scholar]
  7. Spradbery, J.P. Wasps: An Account of the Biology and Natural History of Solitary and Social Wasps; University of Washington Press: Seattle, WA, USA, 1973; p. 408. [Google Scholar]
  8. Hunting Wasp. Available online: (accessed on 16 December 2015).
  9. Tree of Life Web Project. 1995. Aculeata. Version 01 January 1995 (Temporary). Available online: http://tolweb.Org/aculeata/11184/1995.01.01 in the Tree of Life Web Project; http://tolweb.Org/.; (accessed on 17 December 2015).
  10. Clemetson, K.; Kini, R.M. Introduction. In Toxins and Hemostasis: From Bench to Bedside; Kini, R.M., Clemetson, K.J., Markland, F.S., McLane, M.A., Morita, T., Eds.; Springer: Dordrecht, The Netherlands, 2011; pp. 1–9. [Google Scholar]
  11. Fry, B.G.; Roelants, K.; Champagne, D.E.; Scheib, H.; Tyndall, J.D.A.; King, G.F.; Nevalainen, T.J.; Norman, J.A.; Lewis, R.J.; Norton, R.S.; et al. The toxicogenomic multiverse: Convergent recruitment of proteins into animal venoms. Annu. Rev. Genomics Hum. Genet. 2009, 10, 483–511. [Google Scholar] [CrossRef] [PubMed]
  12. Fry, B.G.; Roelants, K.; Norman, J.A. Tentacles of venom: Toxic protein convergence in the Kingdom Animalia. J. Mol. Evol. 2009, 68, 311–321. [Google Scholar] [CrossRef] [PubMed]
  13. Lai, R.; Liu, C. Bioactive peptides and proteins from wasp venoms. In Toxins and Hemostasis: From Bench to Bedside; Kini, R.M., Clemetson, K.J., Markland, F.S., McLane, M.A., Morita, T., Eds.; Springer: Dordrecht, The Netherlands, 2011; pp. 83–96. [Google Scholar]
  14. Palma, M.S. Chapter 56—Insect venom peptides. In Handbook of Biologically Active Peptides; Kastin, A.J., Ed.; Academic Press: Burlington, NJ, USA, 2006; pp. 389–396. [Google Scholar]
  15. National center for biotechnology information. Available online: (accessed on 16 December 2015).
  16. Baek, J.H.; Lee, S.H. Identification and characterization of venom proteins of two solitary wasps. Toxicon 2010, 56, 554–562. [Google Scholar] [CrossRef] [PubMed]
  17. Baek, J.H.; Woo, T.H.; Kim, C.B.; Park, J.H.; Kim, H.; Lee, S.; Lee, S.H. Differential gene expression profiles in the venom gland/sac of Orancistrocerus drewseni (Hymenoptera: Eumenidae). Arch. Insect Biochem. Physiol. 2009, 71, 205–222. [Google Scholar] [CrossRef] [PubMed]
  18. Baek, J.H.; Lee, S.H. Differential gene expression profiles in the venom gland/sac of Eumenes pomiformis (Hymenoptera: Eumenidae). Toxicon 2010, 55, 1147–1156. [Google Scholar] [CrossRef] [PubMed]
  19. Baek, J.H.; Oh, J.H.; Kim, Y.H.; Lee, S.H. Comparative transcriptome analysis of the venom sac and gland of social wasp Vespa tropica and solitary wasp Rhynchium brunneum. J. Asia Pac. Entomol. 2013, 16, 497–502. [Google Scholar] [CrossRef]
  20. Yoon, K.A.; Kim, K.; Nguyen, P.; Seo, J.B.; Park, Y.H.; Kim, K.-G.; Seo, H.-Y.; Koh, Y.H.; Lee, S.H. Comparative functional venomics of social hornets Vespa crabro and Vespa analis. J. Asia Pac. Entomol. 2015, 18, 815–823. [Google Scholar] [CrossRef]
  21. Liu, Z.R.; Chen, S.G.; Zhou, Y.; Xie, C.H.; Zhu, B.F.; Zhu, H.M.; Liu, S.P.; Wang, W.; Chen, H.Z.; Ji, Y.H. Deciphering the venomic transcriptome of killer-wasp Vespa velutina. Sci Rep. 2015, 5. [Google Scholar] [CrossRef] [PubMed]
  22. Dos Santos, L.D.; Santos, K.S.; Pinto, J.R.A.; Dias, N.B.; Souza, B.M.D.; dos Santos, M.F.; Perales, J.; Domont, G.B.; Castro, F.M.; Kalil, J.E.; et al. Profiling the proteome of the venom from the social wasp Polybia paulista: A clue to understand the envenoming mechanism. J. Proteome Res. 2010, 9, 3867–3877. [Google Scholar] [CrossRef] [PubMed]
  23. Konno, K.; Hisada, M.; Itagaki, Y.; Naoki, H.; Kawai, N.; Miwa, A.; Yasuhara, T.; Takayama, H. Isolation and structure of pompilidotoxins, novel peptide neurotoxins in solitary wasp venoms. Biochem. Biophys. Res. Commun. 1998, 250, 612–616. [Google Scholar] [CrossRef] [PubMed]
  24. Konno, K.; Palma, M.S.; Hitara, I.Y.; Juliano, M.A.; Juliano, L.; Yasuhara, T. Identification of bradykinins in solitary wasp venoms. Toxicon 2002, 40, 309–312. [Google Scholar] [CrossRef]
  25. Piek, T. Wasp kinins and kinin analogues. In Animal Toxins: Facts and Protocols; Rochat, H., Martin-Eauclaire, M.-F., Eds.; Birkhauser Verlag: Boston, MA, USA, 2000; pp. 99–115. [Google Scholar]
  26. Piek, T.; Mantel, P.; van Ginkel, C.J.W. Megascoliakinin, a bradykinin-like compound in the venom of Megascolia flavifrons fab. (Hymenoptera: Scoliidae). Comp. Biochem. Physiol. C 1984, 78, 473–474. [Google Scholar] [CrossRef]
  27. Konno, K.; Hisada, M.; Fontana, R.; Lorenzi, C.C.; Naoki, H.; Itagaki, Y.; Miwa, A.; Kawai, N.; Nakata, Y.; Yasuhara, T.; et al. Anoplin, a novel antimicrobial peptide from the venom of the solitary wasp Anoplius samariensis. Biochim. Biophys. Acta 2001, 1550, 70–80. [Google Scholar] [CrossRef]
  28. Konno, K.; Rangel, M.; Oliveira, J.S.; dos Santos Cabrera, M.P.; Fontana, R.; Hirata, I.Y.; Hide, I.; Nakata, Y.; Mori, K.; Kawano, M.; et al. Decoralin, a novel linear cationic α-helical peptide from the venom of the solitary Eumenine wasp Oreumenes decoratus. Peptides 2007, 28, 2320–2327. [Google Scholar] [CrossRef] [PubMed]
  29. Konno, K.; Hisada, M.; Naoki, H.; Itagaki, Y.; Fontana, R.; Rangel, M.; Oliveira, J.S.; Cabreraf, M.P.D.; Neto, J.R.; Hide, I.; et al. Eumenitin, a novel antimicrobial peptide from the venom of the solitary Eumenine wasp Eumenes rubronotatus. Peptides 2006, 27, 2624–2631. [Google Scholar] [CrossRef] [PubMed]
  30. Murata, K.; Shinada, T.; Ohfune, Y.; Hisada, M.; Yasuda, A.; Naoki, H.; Nakajima, T. Novel mastoparan and protonectin analogs isolated from a solitary wasp, Orancistrocerus drewseni drewseni. Amino Acids 2009, 37, 389–394. [Google Scholar] [CrossRef] [PubMed]
  31. Cabrera, M.P.D.; de Souza, B.M.; Fontana, R.; Konno, K.; Palma, M.S.; de Azevedo, W.F.; Neto, J.R. Conformation and lytic activity of Eumenine mastoparan: A new antimicrobial peptide from wasp venom. J. Pept. Res. 2004, 64, 95–103. [Google Scholar] [CrossRef] [PubMed]
  32. Sforca, M.L.; Oyama, S.; Canduri, F.; Lorenzi, C.C.B.; Pertinhez, T.A.; Konno, K.; Souza, B.M.; Palma, N.S.; Neto, J.R.; Azevedo, W.F.; et al. How C-terminal carboxyamidation alters the biological activity of peptides from the venom of the Eumenine solitary wasp. Biochemistry 2004, 43, 5608–5617. [Google Scholar] [CrossRef] [PubMed]
  33. Picolo, G.; Hisada, M.; Moura, A.B.; Machado, M.F.M.; Sciani, J.M.; Conceicao, I.M.; Melo, R.L.; Oliveira, V.; Lima-Landman, M.T.R.; Cury, Y.; et al. Bradykinin-related peptides in the venom of the solitary wasp Cyphononyx fulvognathus. Biochem. Pharmacol. 2010, 79, 478–486. [Google Scholar] [CrossRef] [PubMed]
  34. Yamamoto, T.; Arimoto, H.; Kinumi, T.; Oba, Y.; Uemura, D. Identification of proteins from venom of the paralytic spider wasp, Cyphononyx dorsalis. Insect Biochem. Mol. 2007, 37, 278–286. [Google Scholar] [CrossRef] [PubMed]
  35. De Oliveira, L.; Cunha, A.O.; Mortari, M.R.; Pizzo, A.B.; Miranda, A.; Coimbra, N.C.; dos Santos, W.F. Effects of microinjections of neurotoxin AvTx8, isolated from the social wasp Agelaia vicina (Hymenoptera, Vespidae) venom, on GABAergic nigrotectal pathways. Brain Res. 2005, 1031, 74–81. [Google Scholar] [CrossRef] [PubMed]
  36. Pizzo, A.B.; Beleboni, R.O.; Fontana, A.C.; Ribeiro, A.M.; Miranda, A.; Coutinho-Netto, J.; dos Santos, W.F. Characterization of the actions of AvTx 7 isolated from Agelaia vicina (Hymenoptera: Vespidae) wasp venom on synaptosomal glutamate uptake and release. J. Biochem. Mol. Toxicol. 2004, 18, 61–68. [Google Scholar] [CrossRef] [PubMed]
  37. Tuichibaev, M.U.; Akhmedova, N.U.; Kazakov, I.; Korneev, A.S.; Gagel’gans, A.I. Low molecular weight peptides from the venom of the giant hornet Vespa orientalis. Structure and function. Biokhimiia 1988, 53, 219–226. [Google Scholar] [PubMed]
  38. Cerovsky, V.; Pohl, J.; Yang, Z.; Alam, N.; Attygalle, A.B. Identification of three novel peptides isolated from the venom of the neotropical social wasp Polistes major major. J. Pept. Sci. 2007, 13, 445–450. [Google Scholar] [CrossRef] [PubMed]
  39. Mendes, M.A.; Palma, M.S. Two new bradykinin-related peptides from the venom of the social wasp Protopolybia exigua (saussure). Peptides 2006, 27, 2632–2639. [Google Scholar] [CrossRef] [PubMed]
  40. Dias, N.B.; de Souza, B.M.; Gomes, P.C.; Brigatte, P.; Palma, M.S. Peptidome profiling of venom from the social wasp Polybia paulista. Toxicon 2015, 107, 290–303. [Google Scholar] [CrossRef] [PubMed]
  41. Nakajima, T.; Yasuhara, T.; Horikawa, R.; Pisano, J.; Erspamer, V. A new structural class of biologically active peptide in non-mammals. In Advances in Experimental Medicine and Biology; Abe, K., Moriya, H., Fujii, S., Eds.; Springer: New York, NY, USA, 1989; pp. 215–220. [Google Scholar]
  42. De Souza, B.M.; da Silva, A.V.R.; Resende, V.M.F.; Arcuri, H.A.; dos Santos Cabrera, M.P.; Ruggiero Neto, J.; Palma, M.S. Characterization of two novel polyfunctional mastoparan peptides from the venom of the social wasp Polybia paulista. Peptides 2009, 30, 1387–1395. [Google Scholar] [CrossRef] [PubMed]
  43. Souza, B.M.; Mendes, M.A.; Santos, L.D.; Marques, M.R.; César, L.M.M.; Almeida, R.N.A.; Pagnocca, F.C.; Konno, K.; Palma, M.S. Structural and functional characterization of two novel peptide toxins isolated from the venom of the social wasp Polybia paulista. Peptides 2005, 26, 2157–2164. [Google Scholar] [CrossRef] [PubMed]
  44. Lee, V.S.; Tu, W.C.; Jinn, T.R.; Peng, C.C.; Lin, L.J.; Tzen, J.T. Molecular cloning of the precursor polypeptide of mastoparan B and its putative processing enzyme, dipeptidyl peptidase IV, from the black-bellied hornet, Vespa basalis. Insect Mol. Biol. 2007, 16, 231–237. [Google Scholar] [CrossRef] [PubMed]
  45. Xu, X.; Li, J.; Lu, Q.; Yang, H.; Zhang, Y.; Lai, R. Two families of antimicrobial peptides from wasp (Vespa magnifica) venom. Toxicon 2006, 47, 249–253. [Google Scholar] [CrossRef] [PubMed]
  46. Mendes, M.A.; de Souza, B.M.; Palma, M.S. Structural and biological characterization of three novel mastoparan peptides from the venom of the neotropical social wasp Protopolybia exigua (saussure). Toxicon 2005, 45, 101–106. [Google Scholar] [CrossRef] [PubMed]
  47. Lin, C.H.; Tzen, J.T.C.; Shyu, C.L.; Yang, M.J.; Tu, W.C. Structural and biological characterization of mastoparans in the venom of Vespa species in taiwan. Peptides 2011, 32, 2027–2036. [Google Scholar] [CrossRef] [PubMed]
  48. Ho, C.L.; Hwang, L.L. Structure and biological activities of a new mastoparan isolated from the venom of the hornet Vespa basalis. Biochem. J. 1991, 274, 453–456. [Google Scholar] [CrossRef] [PubMed]
  49. Chen, W.; Yang, X.; Yang, X.; Zhai, L.; Lu, Z.; Liu, J.; Yu, H. Antimicrobial peptides from the venoms of Vespa bicolor fabricius. Peptides 2008, 29, 1887–1892. [Google Scholar] [CrossRef] [PubMed]
  50. Yang, X.W.; Wang, Y.; Lee, W.H.; Zhang, Y. Antimicrobial peptides from the venom gland of the social wasp Vespa tropica. Toxicon 2013, 74, 151–157. [Google Scholar] [CrossRef] [PubMed]
  51. Baptista-Saidemberg, N.B.; Saidemberg, D.M.; Ribeiro, R.A.; Arcuri, H.A.; Palma, M.S.; Carneiro, E.M. Agelaia MP-I: A peptide isolated from the venom of the social wasp, Agelaia pallipes pallipes, enhances insulin secretion in mice pancreatic islets. Toxicon 2012, 60, 596–602. [Google Scholar] [CrossRef] [PubMed]
  52. Mendes, M.A.; de Souza, B.M.; Marques, M.R.; Palma, M.S. Structural and biological characterization of two novel peptides from the venom of the neotropical social wasp Agelaia pallipes pallipes. Toxicon 2004, 44, 67–74. [Google Scholar] [CrossRef] [PubMed]
  53. Piek, T.O.M.; Spanjer, W. 5—Chemistry and pharmacology of solitary wasp venoms. In Venoms of the Hymenoptera: Biochemical, Pharmacological and Behavioural Aspects; Piek, T., Ed.; Academic Press: London, UK, 1986; pp. 161–307. [Google Scholar]
  54. Yu, H.N.; Yang, H.L.; Ma, D.Y.; Lv, Y.; Liu, T.G.; Zhang, K.Y.; Lai, R.; Liu, J.Z. Vespid chemotactic peptide precursor from the wasp, Vespa magnifica (smith). Toxicon 2007, 50, 377–382. [Google Scholar] [CrossRef] [PubMed]
  55. Justo Jacomini, D.L.; Campos Pereira, F.D.; Aparecido dos Santos Pinto, J.R.; dos Santos, L.D.; da Silva Neto, A.J.; Giratto, D.T.; Palma, M.S.; de Lima Zollner, R.; Brochetto Braga, M.R. Hyaluronidase from the venom of the social wasp Polybia paulista (Hymenoptera, Vespidae): Cloning, structural modeling, purification, and immunological analysis. Toxicon 2013, 64, 70–80. [Google Scholar] [CrossRef] [PubMed]
  56. An, S.; Chen, L.; Wei, J.F.; Yang, X.; Ma, D.; Xu, X.; Xu, X.; He, S.; Lu, J.; Lai, R. Purification and characterization of two new allergens from the venom of Vespa magnifica. PLoS ONE 2012, 7. [Google Scholar] [CrossRef] [PubMed]
  57. King, T.P.; Spangfort, M.D. Structure and biology of stinging insect venom allergens. Int. Arch. Allergy Immunol. 2000, 123, 99–106. [Google Scholar] [CrossRef] [PubMed]
  58. Sukprasert, S.; Rungsa, P.; Uawonggul, N.; Incamnoi, P.; Thammasirirak, S.; Daduang, J.; Daduang, S. Purification and structural characterisation of phospholipase A1 (Vespapase, Ves a 1) from thai banded tiger wasp (Vespa affinis) venom. Toxicon 2013, 61, 151–164. [Google Scholar] [CrossRef] [PubMed]
  59. Hoffman, D.R. Allergens in hymenoptera venom 25: The amino-acid-sequences of antigen 5 molecules and the structural basis of antigenic cross-reactivity. J. Allergy Clin. Immunol. 1993, 92, 707–716. [Google Scholar] [CrossRef]
  60. Monsalve, R.I.; Lu, G.; King, T.P. Expressions of recombinant venom allergen, antigen 5 of yellowjacket (Vespula vulgaris) and paper wasp (Polistes annularis), in bacteria or yeast. Protein Expr. Purif. 1999, 16, 410–416. [Google Scholar] [CrossRef] [PubMed]
  61. Henriksen, A.; King, T.P.; Mirza, O.; Monsalve, R.I.; Meno, K.; Ipsen, H.; Larsen, J.N.; Gajhede, M.; Spangfort, M.D. Major venom allergen of yellow jackets, Ves v 5: Structural characterization of a pathogenesis-related protein superfamily. Proteins 2001, 45, 438–448. [Google Scholar] [CrossRef] [PubMed]
  62. King, T.P.; Moran, D.; Wang, D.F.; Kochoumian, L.; Chait, B.T. Structural studies of a hornet venom allergen antigen 5, Dol m V and its sequence similarity with other proteins. Protein Seq. Data Anal. 1990, 3, 263–266. [Google Scholar] [PubMed]
  63. Han, J.Y.; You, D.W.; Xu, X.Q.; Han, W.; Lu, Y.; Lai, R.; Meng, Q.X. An anticoagulant serine protease from the wasp venom of Vespa magnifica. Toxicon 2008, 51, 914–922. [Google Scholar] [CrossRef] [PubMed]
  64. Chen, L.; Chen, W.; Yang, H.; Lai, R. A novel bioactive peptide from wasp venom. J. Venom Res. 2010, 1, 43–47. [Google Scholar] [PubMed]
  65. Yoon, K.A.; Kim, K.; Nguyen, P.; Seo, J.B.; Park, Y.H.; Kim, K.-G.; Seo, H.-Y.; Koh, Y.H.; Lee, S.H. Comparative bioactivities of mastoparans from social hornets Vespa crabro and Vespa analis. J. Asia Pac. Entomol. 2015, 18, 825–829. [Google Scholar] [CrossRef]
  66. Baek, J.H.; Lee, S.H. Isolation and molecular cloning of venom peptides from Orancistrocerus drewseni (Hymenoptera: Eumenidae). Toxicon 2010, 55, 711–718. [Google Scholar] [CrossRef] [PubMed]
  67. Hsu, C.-C.; Huang, T.-F. Biological activities of snake venom metalloproteinases on platelets, neutrophils, endothelial cells, and extracellular matrices. In Toxins and Hemostasis: From Bench to Bedside; Kini, R.M., Clemetson, K.J., Markland, F.S., McLane, M.A., Morita, T., Eds.; Springer: Dordrecht, The Netherlands, 2011; pp. 723–732. [Google Scholar]
  68. Fernandez-Patron, C.; Leung, D. Emergence of a metalloproteinase/phospholipase A2 axis of systemic inflammation. Metalloproteinases Med. 2015, 2, 29–38. [Google Scholar] [CrossRef] [PubMed]
  69. Itino, T. Comparison of life tables between the solitary Eumenid wasp Antherhynchium flavomarginatum and the subsocial Eumenid wasp Orancistrocerus drewseni to evaluate the adaptive significance of maternal care. Res. Popul. Ecol. 1986, 28, 185–199. [Google Scholar] [CrossRef]
  70. Munoz-Torres, M.C.; Reese, J.T.; Childers, C.P.; Bennett, A.K.; Sundaram, J.P.; Childs, K.L.; Anzola, J.M.; Milshina, N.; Elsik, C.G. Hymenoptera genome database: Integrated community resources for insect species of the order Hymenoptera. Nucleic Acids Res. 2011, 39, D658–D662. [Google Scholar] [CrossRef] [PubMed]
  71. Heavner, M.E.; Gueguen, G.; Rajwani, R.; Pagan, P.E.; Small, C.; Govind, S. Partial venom gland transcriptome of a Drosophila parasitoid wasp, Leptopilina heterotoma, reveals novel and shared bioactive profiles with stinging Hymenoptera. Gene 2013, 526, 195–204. [Google Scholar] [CrossRef] [PubMed]
  72. Zhu, J.Y.; Fang, Q.; Wang, L.; Hu, C.; Ye, G.Y. Proteomic analysis of the venom from the endoparasitoid wasp Pteromalus puparum (Hymenoptera: Pteromalidae). Arch. Insect Biochem. 2010, 75, 28–44. [Google Scholar] [CrossRef] [PubMed]
  73. Kreil, G. Hyaluronidases—A group of neglected enzymes. Protein Sci. 1995, 4, 1666–1669. [Google Scholar] [CrossRef] [PubMed]
  74. Kemparaju, K.; Girish, K.S. Snake venom hyaluronidase: A therapeutic target. Cell Biochem. Funct. 2006, 24, 7–12. [Google Scholar] [CrossRef] [PubMed]
  75. Nagaraju, S.; Devaraja, S.; Kemparaju, K. Purification and properties of hyaluronidase from Hippasa partita (funnel web spider) venom gland extract. Toxicon 2007, 50, 383–393. [Google Scholar] [CrossRef] [PubMed]
  76. Girish, K.S.; Kemparaju, K. The magic glue hyaluronan and its eraser hyaluronidase: A biological overview. Life Sci. 2007, 80, 1921–1943. [Google Scholar] [CrossRef] [PubMed]
  77. Konno, K.; Miwa, A.; Takayama, H.; Hisada, M.; Itagaki, Y.; Naoki, H.; Yasuhara, T.; Kawai, N. Alpha-pompilidotoxin (α-pmtx), a novel neurotoxin from the venom of a solitary wasp, facilitates transmission in the crustacean neuromuscular synapse. Neurosci. Lett. 1997, 238, 99–102. [Google Scholar] [CrossRef]
  78. Sahara, Y.; Gotoh, M.; Konno, K.; Miwa, A.; Tsubokawa, H.; Robinson, H.P.; Kawai, N. A new class of neurotoxin from wasp venom slows inactivation of sodium current. Eur. J. Neurosci. 2000, 12, 1961–1970. [Google Scholar] [CrossRef] [PubMed]
  79. Hisada, M.; Satake, H.; Masuda, K.; Aoyama, M.; Murata, K.; Shinada, T.; Iwashita, T.; Ohfune, Y.; Nakajima, T. Molecular components and toxicity of the venom of the solitary wasp, Anoplius samariensis. Biochem. Biophys. Res. Commun. 2005, 330, 1048–1054. [Google Scholar] [CrossRef] [PubMed]
  80. Piek, T. Delta-philanthotoxin, a semi-irreversible blocker of ion-channels. Comp. Biochem. Phys. C 1982, 72, 311–315. [Google Scholar] [CrossRef]
  81. Vanmarle, J.; Piek, T.; Lind, A.; Vanweerenkramer, J. Inhibition of the glutamate uptake in the excitatory neuromuscular synapse of the locust by delta-philanthotoxin—A component of the venom of the solitary wasp Philanthus-triangulum f a high-resolution autoradiographic study. Comp. Biochem Phys. C 1984, 79, 213–215. [Google Scholar] [CrossRef]
  82. Piek, T.; Hue, B.; Pelhate, M.; David, J.A.; Spanjer, W.; Veldsemacurrie, R.D. Effects of the venom of Philanthus triangulum F. (Hym-Sphecidae) and beta-philanthotoxin and delta-philanthotoxin on axonal excitability and synaptic transmission in the cockroach CNS. Arch. Insect Biochem. 1984, 1, 297–306. [Google Scholar] [CrossRef]
  83. Moore, E.L.; Haspel, G.; Libersat, F.; Adams, M.E. Parasitoid wasp sting: A cocktail of GABA, taurine, and beta-alanine opens chloride channels for central synaptic block and transient paralysis of a cockroach host. J. Neurobiol. 2006, 66, 811–820. [Google Scholar] [CrossRef] [PubMed]
  84. Baek, J.H.; Lee, S.H.; Kim, W.-Y.; Kim, M.G. An insulin-binding protein from the venom of a solitary wasp Eumenes pomiformis binds to apolipophorin III in Lepidopteran hemolymph. Toxicon 2016, 111, 62–64. [Google Scholar] [CrossRef] [PubMed]
  85. Danneels, E.L.; Rivers, D.B.; de Graaf, D.C. Venom proteins of the parasitoid wasp Nasonia vitripennis: Recent discovery of an untapped pharmacopee. Toxins 2010, 2, 494–516. [Google Scholar] [CrossRef] [PubMed][Green Version]
  86. Lee, K.M.; Lee, K.Y.; Choi, H.W.; Cho, M.Y.; Kwon, T.H.; Kawabata, S.; Lee, B.L. Activated phenoloxidase from tenebrio molitor larvae enhances the synthesis of melanin by using a vitellogenin-like protein in the presence of dopamine. Eur. J. Biochem. 2000, 267, 3695–3703. [Google Scholar] [CrossRef] [PubMed]
  87. Fang, K.S.Y.; Vitale, M.; Fehlner, P.; King, T.P. CDNA cloning and primary structure of a white-face hornet venom allergen, antigen-5. Proc. Natl. Acad. Sci. USA 1988, 85, 895–899. [Google Scholar] [CrossRef] [PubMed]
  88. Vincent, B.; Kaeslin, M.; Roth, T.; Heller, M.; Poulain, J.; Cousserans, F.; Schaller, J.; Poirie, M.; Lanzrein, B.; Drezen, J.M.; et al. The venom composition of the parasitic wasp Chelonus inanitus resolved by combined expressed sequence tags analysis and proteomic approach. BMC Genomics 2010, 11. [Google Scholar] [CrossRef] [PubMed][Green Version]
  89. Hoffman, D.R. Hymenoptera venom allergens. Clin. Rev. Allergy Immunol. 2006, 30, 109–128. [Google Scholar] [CrossRef]
  90. Barboni, E.; Kemeny, D.M.; Campos, S.; Vernon, C.A. The purification of acid-phosphatase from honey-bee venom (Apis-mellifica). Toxicon 1987, 25, 1097–1103. [Google Scholar] [CrossRef]
  91. Kim, B.Y.; Jin, B.R. Molecular characterization of a venom acid phosphatase Acph-1-like protein from the Asiatic honeybee Apis cerana. J. Asia Pac. Entomol. 2014, 17, 695–700. [Google Scholar] [CrossRef]
  92. Hoffman, D.R. Allergens in bee venom: III. Identification of allergen-B of bee venom as an acid-phosphatase. J. Allergy Clin. Immunol. 1977, 59, 364–366. [Google Scholar] [CrossRef]
  93. De Graaf, D.C.; Aerts, M.; Brunain, M.; Desjardins, C.A.; Jacobs, F.J.; Werren, J.H.; Devreese, B. Insights into the venom composition of the ectoparasitoid wasp Nasonia vitripennis from bioinformatic and proteomic studies. Insect Mol. Biol. 2010, 19, 11–26. [Google Scholar] [CrossRef] [PubMed]
  94. Grunwald, T.; Bockisch, B.; Spillner, E.; Ring, J.; Bredehorst, R.; Ollert, M.W. Molecular cloning and expression in insect cells of honeybee venom allergen acid phosphatase (Api m 3). J. Allergy Clin. Immunol. 2006, 117, 848–854. [Google Scholar] [CrossRef] [PubMed]
  95. The Chemical Compositions of Insect Venoms. Available online: (accessed on 18 December 2015).
  96. Yang, J.; Zhao, Y.; Pan, Y.; Lu, G.; Lu, L.; Wang, D.; Wang, J. Acetylcholine participates in pain modulation by influencing endogenous opiate peptides in rat spinal cord. World J. Neurosci. 2012, 2, 15–22. [Google Scholar] [CrossRef]
  97. Gorrell, M.D. Dipeptidyl peptidase iv and related enzymes in cell biology and liver disorders. Clin. Sci. (Lond.) 2005, 108, 277–292. [Google Scholar] [CrossRef] [PubMed]
  98. Eipper, B.A.; Milgram, S.L.; Husten, E.J.; Yun, H.Y.; Mains, R.E. Peptidylglycine alpha-amidating monooxygenase: A multifunctional protein with catalytic, processing, and routing domains. Protein Sci. 1993, 2, 489–497. [Google Scholar] [CrossRef] [PubMed]
  99. Kreil, G.; Kreil-Kiss, G. The isolation of N-formylglycine from a polypeptide present in bee venom. Biochem. Biophys. Res. Commun. 1967, 27, 275–280. [Google Scholar] [CrossRef]
  100. Schachter, M.; Thain, E.M. Chemical and pharmacological properties of the potent, slow contracting substance (kinin) in wasp venom. Br. J. Pharmacol. Chemother. 1954, 9, 352–359. [Google Scholar] [CrossRef] [PubMed]
  101. Nakajima, T. Pharmacological biochemistry of vespid venoms. In Venoms of the Hymenoptera: Biochemical, Pharmacological and Behavioural Aspects; Piek, T., Ed.; Academic: London, UK, 1986; pp. 309–327. [Google Scholar]
  102. Rocha, E.S.M.; Beraldo, W.T.; Rosenfeld, G. Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin. Am. J. Physiol. 1949, 156, 261–273. [Google Scholar]
  103. Podvin, S.; Bundey, R.; Toneff, T.; Ziegler, M.; Hook, V. Profiles of secreted neuropeptides and catecholamines illustrate similarities and differences in response to stimulation by distinct secretagogues. Mol. Cell. Neurosci. 2015, 68, 177–185. [Google Scholar] [CrossRef] [PubMed]
  104. Piek, T.; Hue, B.; Pelhate, M.; Mony, L. The venom of the wasp Campsomeris sexmaculata (F.) blocks synaptic transmission in insect CNS. Comp. Biochem. Physiol. C 1987, 87, 283–286. [Google Scholar] [CrossRef]
  105. Piek, T.; Hue, B.; Mantel, P.; Nakajima, T.; Pelhate, M.; Yasuhara, T. Threonine6-bradykinin in the venom of the wasp Colpa interrupta (F.) presynaptically blocks nicotinic synaptic transmission in the insect CNS. Comp. Biochem. Physiol. C 1990, 96, 157–162. [Google Scholar] [CrossRef]
  106. Mortari, M.R.; Cunha, A.O.; Carolino, R.O.; Coutinho-Netto, J.; Tomaz, J.C.; Lopes, N.P.; Coimbra, N.C.; dos Santos, W.F. Inhibition of acute nociceptive responses in rats after i.c.v. Injection of Thr6-bradykinin, isolated from the venom of the social wasp, Polybia occidentalis. Br. J. Pharmacol. 2007, 151, 860–869. [Google Scholar] [CrossRef] [PubMed]
  107. Konno, K.; Hisada, M.; Naoki, H.; Itagaki, Y.; Yasuhara, T.; Juliano, M.A.; Juliano, L.; Palma, M.S.; Yamane, T.; Nakajima, T. Isolation and sequence determination of peptides in the venom of the spider wasp (Cyphononyx dorsalis) guided by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. Toxicon 2001, 39, 1257–1260. [Google Scholar] [CrossRef]
  108. Alsop, D.W.; Bettini, S. Arthropod Venoms; Springer-Verlag: Berlin, Germany; New York, NY, USA, 1978; p. 977. [Google Scholar]
  109. Piek, T.; Hue, B.; Lind, A.; Mantel, P.; van Marle, J.; Visser, J.H. The venom of ampulex compressa—Effects on behaviour and synaptic transmission of cockroaches. Comp. Biochem. Physiol. C 1989, 92, 175–183. [Google Scholar] [CrossRef]
  110. Hirai, Y.; Yasuhara, T.; Yoshida, H.; Nakajima, T.; Fujino, M.; Kitada, C. A new mast cell degranulating peptide “mastoparan” in the venom of Vespula lewisii. Chem. Pharm. Bull. 1979, 27, 1942–1944. [Google Scholar] [CrossRef] [PubMed]
  111. Brogden, K.A. Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 2005, 3, 238–250. [Google Scholar] [CrossRef] [PubMed]
  112. Higashijima, T.; Uzu, S.; Nakajima, T.; Ross, E.M. Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins). J. Biol. Chem. 1988, 263, 6491–6494. [Google Scholar] [PubMed]
  113. Kurihara, H.; Kitajima, K.; Senda, T.; Fujita, H.; Nakajima, T. Multigranular exocytosis induced by phospholipase A2-activators, melittin and mastoparan, in rat anterior pituitary cells. Cell Tissue Res. 1986, 243, 311–316. [Google Scholar] [CrossRef] [PubMed]
  114. Baek, J.H.; Ji, Y.; Shin, J.S.; Lee, S.; Lee, S.H. Venom peptides from solitary hunting wasps induce feeding disorder in Lepidopteran larvae. Peptides 2011, 32, 568–572. [Google Scholar] [CrossRef] [PubMed]
  115. Moreno, M.; Giralt, E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: Melittin, apamin and mastoparan. Toxins 2015, 7, 1126–1150. [Google Scholar] [CrossRef] [PubMed]
  116. Rocha, T.; de Souza, B.M.; Palma, M.S.; da Cruz-Hofling, M.A. Myotoxic effects of mastoparan from Polybia paulista (Hymenoptera, Epiponini) wasp venom in mice skeletal muscle. Toxicon 2007, 50, 589–599. [Google Scholar] [CrossRef] [PubMed]
  117. Silva, J.; Monge-Fuentes, V.; Gomes, F.; Lopes, K.; dos Anjos, L.; Campos, G.; Arenas, C.; Biolchi, A.; Goncalves, J.; Galante, P.; et al. Pharmacological alternatives for the treatment of neurodegenerative disorders: Wasp and bee venoms and their components as new neuroactive tools. Toxins 2015, 7, 3179–3209. [Google Scholar] [CrossRef] [PubMed]
  118. Moreno, M.; Zurita, E.; Giralt, E. Delivering wasp venom for cancer therapy. J. Control. Release 2014, 182, 13–21. [Google Scholar] [CrossRef] [PubMed]
  119. Kastin, A.J. Handbook of Biologically Active Peptides; Academic Press: Amsterdam, The Netherlands; Boston, MA, USA, 2006; p. 1595. [Google Scholar]
  120. Jindrichova, B.; Burketova, L.; Novotna, Z. Novel properties of antimicrobial peptide anoplin. Biochem. Biophys. Res. Commun. 2014, 444, 520–524. [Google Scholar] [CrossRef] [PubMed]
  121. Ifrah, D.; Doisy, X.; Ryge, T.S.; Hansen, P.R. Structure-activity relationship study of anoplin. J. Pept. Sci. 2005, 11, 113–121. [Google Scholar] [CrossRef] [PubMed]
  122. Spillner, E.; Blank, S.; Jakob, T. Hymenoptera allergens: From venom to “venome”. Front. Immunol. 2014, 5. [Google Scholar] [CrossRef] [PubMed]
  123. Boyle, R.J.; Elremeli, M.; Hockenhull, J.; Cherry, M.G.; Bulsara, M.K.; Daniels, M.; Elberink, J.N.G.O. Venom immunotherapy for preventing allergic reactions to insect stings. Cochrane Database Syst. Rev. 2012, 10. [Google Scholar] [CrossRef]
  124. Beckage, N.E.; Gelman, D.B. Wasp parasitoid disruption of host development: Implications for new biologically based strategies for insect control. Annu. Rev. Entomol. 2004, 49, 299–330. [Google Scholar] [CrossRef] [PubMed]
  125. Rydlo, T.; Miltz, J.; Mor, A. Eukaryotic antimicrobial peptides: Promises and premises in food safety. J. Food Sci. 2006, 71, R125–R135. [Google Scholar] [CrossRef]
  126. Bulet, P.; Stocklin, R.; Menin, L. Anti-microbial peptides: From invertebrates to vertebrates. Immunol. Rev. 2004, 198, 169–184. [Google Scholar] [CrossRef] [PubMed]
  127. Reddy, K.V.R.; Yedery, R.D.; Aranha, C. Antimicrobial peptides: Premises and promises. Int. J. Antimicrob. Agents 2004, 24, 536–547. [Google Scholar] [CrossRef] [PubMed]
  128. Vasilev, K.; Cook, J.; Griesser, H.J. Antibacterial surfaces for biomedical devices. Expert Rev. Med. Devices 2009, 6, 553–567. [Google Scholar] [CrossRef] [PubMed]
  129. Basu, A.; Mishra, B.; Leong, S.S.J. Immobilization of polybia-mpi by allyl glycidyl ether based brush chemistry to generate a novel antimicrobial surface. J. Mater. Chem. B 2013, 1, 4746–4755. [Google Scholar] [CrossRef]
  130. Jones, S.; Howl, J. Charge delocalisation and the design of novel mastoparan analogues: Enhanced cytotoxicity and secretory efficacy of [Lys5, Lys8, Aib10]MP. Regul. Pept. 2004, 121, 121–128. [Google Scholar] [CrossRef] [PubMed]
  131. Jones, S.; Martel, C.; Belzacq-Casagrande, A.S.; Brenner, C.; Howl, J. Mitoparan and target-selective chimeric analogues: Membrane translocation and intracellular redistribution induces mitochondrial apoptosis. Biochim. Biophys. Acta 2008, 1783, 849–863. [Google Scholar] [CrossRef] [PubMed]
  132. Wang, K.R.; Zhang, B.Z.; Zhang, W.; Yan, J.X.; Li, J.; Wang, R. Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide Polybia-MPI. Peptides 2008, 29, 963–968. [Google Scholar] [CrossRef] [PubMed]
  133. Wang, K.R.; Yan, J.X.; Zhang, B.Z.; Song, J.J.; Jia, P.F.; Wang, R. Novel mode of action of Polybia-MPI, a novel antimicrobial peptide, in multi-drug resistant leukemic cells. Cancer Lett. 2009, 278, 65–72. [Google Scholar] [CrossRef] [PubMed]
  134. Leite, N.B.; Aufderhorst-Roberts, A.; Palma, M.S.; Connell, S.D.; Neto, J.R.; Beales, P.A. PE and PS lipids synergistically enhance membrane poration by a peptide with anticancer properties. Biophys. J. 2015, 109, 936–947. [Google Scholar] [CrossRef] [PubMed]
  135. Aalberse, R.C.; Akkerdaas, J.H.; van Ree, R. Cross-reactivity of ige antibodies to allergens. Allergy 2001, 56, 478–490. [Google Scholar] [CrossRef] [PubMed]
  136. Muller, U.R. Recombinant Hymenoptera venom allergens. Allergy 2002, 57, 570–576. [Google Scholar] [CrossRef] [PubMed]
  137. Muller, U.; Fricker, M.; Wymann, D.; Blaser, K.; Crameri, R. Increased specificity of diagnostic tests with recombinant major bee venom allergen phospholipase A2. Clin. Exp. Allergy 1997, 27, 915–920. [Google Scholar] [CrossRef] [PubMed]
  138. Magloire, V.; Czarnecki, A.; Anwander, H.; Streit, J. Beta-pompilidotoxin modulates spontaneous activity and persistent sodium currents in spinal networks. Neuroscience 2011, 172, 129–138. [Google Scholar] [CrossRef] [PubMed]
  139. Quistad, G.B.; Nguyen, Q.; Bernasconi, P.; Leisy, D.J. Purification and characterization of insecticidal toxins from venom glands of the parasitic wasp, Bracon hebetor. Insect Biochem. Mol. 1994, 24, 955–961. [Google Scholar] [CrossRef]
  140. Smith, J.J.; Herzig, V.; King, G.F.; Alewood, P.F. The insecticidal potential of venom peptides. Cell. Mol. Life Sci. 2013, 70, 3665–3693. [Google Scholar] [CrossRef] [PubMed]
  141. Down, R.E.; Fitches, E.C.; Wiles, D.P.; Corti, P.; Bell, H.A.; Gatehouse, J.A.; Edwards, J.P. Insecticidal spider venom toxin fused to snowdrop lectin is toxic to the peach-potato aphid, Myzus persicae (Hemiptera: Aphididae) and the rice brown planthopper, Nilaparvata lugens (Hemiptera : Delphacidae). Pest. Manag. Sci. 2006, 62, 77–85. [Google Scholar] [CrossRef] [PubMed]
  142. Fitches, E.C.; Pyati, P.; King, G.F.; Gatehouse, J.A. Fusion to snowdrop lectin magnifies the oral activity of insecticidal omega-hexatoxin-Hv1a peptide by enabling its delivery to the central nervous system. PLoS ONE 2012, 7. [Google Scholar] [CrossRef][Green Version]
  143. Nakasu, E.Y.T.; Williamson, S.M.; Edwards, M.G.; Fitches, E.C.; Gatehouse, J.A.; Wright, G.A.; Gatehouse, A.M.R. Novel biopesticide based on a spider venom peptide shows no adverse effects on honeybees. Proc. Biol. Sci. 2014, 281. [Google Scholar] [CrossRef] [PubMed][Green Version]
  144. Mccutchen, B.F.; Choudary, P.V.; Crenshaw, R.; Maddox, D.; Kamita, S.G.; Palekar, N.; Volrath, S.; Fowler, E.; Hammock, B.D.; Maeda, S. Development of a recombinant baculovirus expressing an insect-selective neurotoxin—Potential for pest-control. Biotechnology 1991, 9, 848–852. [Google Scholar] [CrossRef] [PubMed]
  145. Piek, T.; Hue, B.; Mony, L.; Nakajima, T.; Pelhate, M.; Yasuhara, T. Block of synaptic transmission in insect CNS by toxins from the venom of the wasp Megascolia flavifrons (Fab.). Comp. Biochem. Physiol. C 1987, 87, 287–295. [Google Scholar] [CrossRef]
  146. Kishimura, H.; Yasuhara, T.; Yoshida, H.; Nakajima, T. Vespakinin-M, a novel bradykinin analogue containing hydroxyproline, in the venom of Vespa mandarinia smith. Chem. Pharm. Bull. (Tokyo) 1976, 24, 2896–2897. [Google Scholar] [CrossRef] [PubMed]
  147. Yasuhara, T.; Yoshida, H.; Nakajima, T. Chemical investigation of the hornet (Vespa xanthoptera cameron) venom. The structure of a new bradykinin analogue “vespakinin-X”. Chem. Pharm. Bull. 1977, 25, 936–941. [Google Scholar] [CrossRef] [PubMed]
  148. Gobbo, M.; Biondi, L.; Filira, F.; Rocchi, R.; Piek, T. Cyclic analogues of wasp kinins from Vespa analis and Vespa tropica. Int. J. Pept. Protein Res. 1995, 45, 282–289. [Google Scholar] [CrossRef] [PubMed]
  149. Yoshida, H.; Pisano, J. Vespula kinins: New carbohydrate-containing bradykinin analogues. In Animal, Plant, and Microbial Toxins; Ohsaka, A., Hayashi, K., Sawai, Y., Murata, R., Funatsu, M., Tamiya, N., Eds.; Springer: New York, NY, USA, 1976; pp. 113–121. [Google Scholar]
  150. Konno, K.; Hisada, M.; Naoki, H.; Itagaki, Y.; Kawai, N.; Miwa, A.; Yasuhara, T.; Morimoto, Y.; Nakata, Y. Structure and biological activities of Eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado). Toxicon 2000, 38, 1505–1515. [Google Scholar] [CrossRef]
  151. Dohtsu, K.; Okumura, K.; Hagiwara, K.; Palma, M.S.; Nakajima, T. Isolation and sequence analysis of peptides from the venom of Protonectarina sylveirae (Hymenoptera-Vespidae). Nat. Toxins 1993, 1, 271–276. [Google Scholar] [CrossRef] [PubMed]
  152. Baptista-Saidemberg, N.B.; Saidemberg, D.M.; de Souza, B.M.; Cesar-Tognoli, L.M.; Ferreira, V.M.; Mendes, M.A.; Cabrera, M.P.; Ruggiero Neto, J.; Palma, M.S. Protonectin (1–6): A novel chemotactic peptide from the venom of the social wasp Agelaia pallipes pallipes. Toxicon 2010, 56, 880–889. [Google Scholar] [CrossRef] [PubMed]
  153. Krishnakumari, V.; Nagaraj, R. Antimicrobial and hemolytic activities of crabrolin, a 13-residue peptide from the venom of the European hornet, Vespa crabro, and its analogs. J. Pept. Res. 1997, 50, 88–93. [Google Scholar] [CrossRef] [PubMed]
  154. Ho, C.L.; Chen, W.C.; Lin, Y.L. Structures and biological activities of new wasp venom peptides isolated from the black-bellied hornet (Vespa basalis) venom. Toxicon 1998, 36, 609–617. [Google Scholar] [CrossRef]
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