It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula

Samantha A Nixon; Zoltan Dekan; Samuel D Robinson; Shaodong Guo; Irina Vetter; Andrew C Kotze; Paul F Alewood; Glenn F King; Volker Herzig

doi:10.3390/biomedicines8070185

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It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula

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It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula

Samantha A Nixon, Zoltan Dekan, Samuel D Robinson, Shaodong Guo, Irina Vetter, Andrew C Kotze, Paul F Alewood, Glenn F King and Volker Herzig

Biomedicines, Vol.8(7), pp.1-13

2020

DOI: https://doi.org/10.3390/biomedicines8070185

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Abstract

ant

venom

venom peptide

pilosulin

heterodimer

antiparasitic

antimicrobial

Ant venoms have recently attracted increased attention due to their chemical complexity, novel molecular frameworks, and diverse biological activities. The heterodimeric peptide ∆-myrtoxin-Mp1a (Mp1a) from the venom of the Australian jack jumper ant, Myrmecia pilosula, exhibits antimicrobial, membrane-disrupting, and pain-inducing activities. In the present study, we examined the activity of Mp1a and a panel of synthetic analogues against the gastrointestinal parasitic nematode Haemonchus contortus, the fruit fly Drosophila melanogaster, and for their ability to stimulate pain-sensing neurons. Mp1a was found to be both insecticidal and anthelmintic, and it robustly activated mammalian sensory neurons at concentrations similar to those reported to elicit antimicrobial and cytotoxic activity. The native antiparallel Mp1a heterodimer was more potent than heterodimers with alternative disulfide connectivity, as well as monomeric analogues. We conclude that the membrane-disrupting effects of Mp1a confer broad-spectrum biological activities that facilitate both predation and defense for the ant. Our structure–activity data also provide a foundation for the rational engineering of analogues with selectivity for particular cell types.

Details

Title: It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
Authors: Samantha A Nixon (Author) - The University of Queensland
Zoltan Dekan (Author) - The University of Queensland
Samuel D Robinson (Author) - The University of Queensland
Shaodong Guo (Author) - The University of Queensland
Irina Vetter (Author) - CSIRO Agriculture and Food (Australia)
Andrew C Kotze (Author) - CSIRO Agriculture and Food (Australia)
Paul F Alewood (Author) - The University of Queensland
Glenn F King (Author) - The University of Queensland
Volker Herzig (Author) - University of the Sunshine Coast, Queensland, School of Science and Engineering - Legacy
Publication details: Biomedicines, Vol.8(7), pp.1-13
Publisher: MDPI AG
Date published: 2020
DOI: 10.3390/biomedicines8070185
ISSN: 2227-9059
Copyright note: Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Grants: Be(e) friendly venomous spiders! Novel biopesticides from arachnid venoms, FT190100482, Australian Research Council (Australia, Canberra) - ARC
Discovery and development of better pain treatments, 1072113, National Health and Medical Research Council (Australia, Canberra) - NHMRC
The role of ion channels in pain pathways, 1162503, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Venoms to drugs: translating venom peptides into human therapeutics, 1136889, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Gain from pain: new tools from venomous animals for exploring pain pathways, DP190103787, Australian Research Council (Australia, Canberra) - ARC
Grant note: Westpac Bicentennial Foundation (Westpac Future Leaders Scholarship to S.A.N.)
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99469908702621
Output Type: Journal article

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Collaboration types: Domestic collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Medicine, Research & Experimental; Pharmacology & Pharmacy

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