Whereas adult butterflies and moths are specialised for dispersal and mating, their larvae—caterpillars—are devoted to eating and growth. This otherwise enviable life history leaves the caterpillar with a problem: how can it defend itself from predators while exposed on the leaves it eats, without natural defenses such as teeth or claws, and unable to flee? To solve this problem, caterpillars have evolved a multitude of biological defenses: irritative hairs, toxins that render them poisonous to eat, adhesive droplets, or spines that inject pain-inducing liquid venoms.

Previous studies on caterpillar venoms have focused on the South American saturniid Lonomia obliqua, because their venom is capable of killing humans through haemostatic disruption. However, most caterpillar venoms do not produce either haemostatic disturbances or death, but instead produce intense pain and avoidance responses that deter potential vertebrate and invertebrate predators. In addition, phylogenetic and trait analysis across Lepidoptera strongly suggests venom use has evolved independently at least three times, suggesting other groups of venomous caterpillars are likely to have different venom compositions compared to L. obliqua.

I will present data recently collected from venoms of five species of Australian caterpillar in the family Limacodidae (nettle caterpillars). The venom of each species comprises a combinatorial library of more than 100 individual peptide toxins, with minimal content of proteins >10 kDa or enzymes. Three major groups of peptides are evident, including (1) modified versions of insect neuropeptide hormones whose normal function is neuroendocrine signalling through G-protein coupled receptors (GPCRs); (2) disulfide-rich knottins, a class of peptides found in diverse animal venoms that frequently modulate the activity of neuronal ion channels; and (3) linear amphipathic peptides predicted to take helical structures, similar to venom peptides of hymenopteran insects. I will also discuss our current progress in characterising the structure and function of these peptides, and determining the mechanisms by which they induce pain when injected into vertebrates.