Oral Presentation 8th Venoms to Drugs 2023

Structure, function, and evolution of toxins produces by nettle caterpillar (Limacodidae) (#29)

Mohaddeseh H Goudarzi 1 2 , Samuel D Robinson 1 , Fernanda C Cardoso 1 2 , Nicole Lawrence 1 2 , David A Eagles 1 2 , Yanni K.-Y. Chin 1 2 , Glenn F King 1 2 , Andrew A Walker 1 2
  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld, Australia
  2. Institute for Molecular Biosciences, Australian Research Council Centre of Excellence for Innovations in Protein and Peptide Science, Brisbane, Qld, Australia

Insects mostly use their venom to subdue prey, or for both subduing prey and defense, but some rare species such as larval lepidopterans (caterpillars) use venom solely for deterring predators. Of the 133 lepidopteran families, nine can cause serious pathophysiological conditions in humans. Although they present a health hazard, caterpillars are under-represented in venom research and little is known about their venom composition.

Limacodidae is a family of more than 1,500 species, over half of which have venomous larvae (1). Envenomation by limacodids causes pain, itch, and erythema, and occasionally numbness, nausea, and dizziness. Using a combination of imaging technologies, transcriptomics, proteomics and functional assays, we recently provided a portrait of the venom of one species, Doratifera vulnerans, which produces a complex peptide-rich venom, contrary to the common belief that defensive venoms are simple (2). Three of the most abundant peptide families are:

-disulfide-rich knottins similar to the inhibitor cystine knot (ICK) peptides;

-linear, cationic cecropin-like peptides that cause pain in mammals, and kill bacteria and parasites; and

-homologues of adipokinetic hormone/corazonin-related neuropeptide (ACPs) (2).

Using proteomics and transcriptomics, I am currently examining the venom of additional species, including the saddleback caterpillar Acharia stimulea native to North America, and Comana monomorpha, from Australia. Surprisingly, I found that the North American species possesses very similar venom to that of the Australian D. vulnerans (3), whereas venom of the other Australian species is radically different, hinting at complex evolution of venom within Limacodidae. I am also expanding knowledge of the evolutionary trajectory of individual toxins, by synthesising and characterising peptides intermediate in structure between the ancestral cecropin of non-venomous Lepidoptera and D. vulnerans cecropin-like venom toxins. Finally, I am producing a library of limacodid venom peptides using solid-phase peptide synthesis and recombinant expression that I will test on different mammalian ion channels.

  1. Epstein M, ed. (1996) Revision and phylogeny of the Limacodid-group families, with evolutionary studies on slug caterpillars (Lepidoptera:Zygaenoidea), Smithsonian Institution Press, Washington DC.
  2. Walker AA, Robinson SD, Paluzzi JV, Merritt DJ, Nixon SA, Schroeder CI, et al. (2021) Production, composition, and mode of action of the painful defensive venom produced by a limacodid caterpillar, Doratifera vulnerans. Proc Natl Acad Sci USA. 118, e2023815118.
  3. Goudarzi MH, Eagles DA, Lim J, Biggs KA, et al. (2023) Venom composition and bioactive RF-amide peptide toxins of the saddleback caterpillar, Acharia stimulea (Lepidoptera: Limacodidae),Biochemical Pharmacology, Volume 213.