A peptide toxin in ant venom mimics vertebrate EGF-like hormones to cause long-lasting hypersensitivity in mammals

David A Eagles; Natalie J Saez; Bankala Krishnarjuna; Julia J Bradford; Yanni K-Y Chin; Hana Starobova; Alexander Mueller; Melissa E Reichelt; Eivind A B Undheim; Raymond S Norton; Walter G Thomas; Irina Vetter; Glenn F King; Samuel D Robinson

doi:10.1073/pnas.2112630119

A peptide toxin in ant venom mimics vertebrate EGF-like hormones to cause long-lasting hypersensitivity in mammals

Proc Natl Acad Sci U S A. 2022 Feb 15;119(7):e2112630119. doi: 10.1073/pnas.2112630119.

Authors

David A Eagles¹, Natalie J Saez^{1

2}, Bankala Krishnarjuna³, Julia J Bradford⁴, Yanni K-Y Chin¹, Hana Starobova¹, Alexander Mueller¹, Melissa E Reichelt⁴, Eivind A B Undheim^{5

6}, Raymond S Norton^{3

7}, Walter G Thomas⁴, Irina Vetter^{1

8}, Glenn F King^{1

2}, Samuel D Robinson⁹

Affiliations

¹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
² Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD 4072, Australia.
³ Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
⁴ School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
⁵ Centre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
⁶ Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
⁷ Australian Research Council Centre for Fragment-Based Design, Monash University, Parkville, VIC 3052, Australia.
⁸ School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia.
⁹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; sam.robinson@uq.edu.au.

Abstract

Venoms are excellent model systems for studying evolutionary processes associated with predator-prey interactions. Here, we present the discovery of a peptide toxin, MIITX₂-Mg1a, which is a major component of the venom of the Australian giant red bull ant Myrmecia gulosa and has evolved to mimic, both structurally and functionally, vertebrate epidermal growth factor (EGF) peptide hormones. We show that Mg1a is a potent agonist of the mammalian EGF receptor ErbB1, and that intraplantar injection in mice causes long-lasting hypersensitivity of the injected paw. These data reveal a previously undescribed venom mode of action, highlight a role for ErbB receptors in mammalian pain signaling, and provide an example of molecular mimicry driven by defensive selection pressure.

Keywords: EGFR; ErbB; Gilbertian mimicry; convergent evolution; mimicry.

MeSH terms

Amino Acid Sequence
Animals
Ant Venoms / chemistry*
Ants / physiology*
Drug Hypersensitivity*
Epidermal Growth Factor / chemistry*
Insect Bites and Stings
Mice
Molecular Mimicry
Toxins, Biological / chemistry*

Substances

Ant Venoms
Toxins, Biological
Epidermal Growth Factor