Multipurpose peptides: The venoms of Amazonian stinging ants contain anthelmintic ponericins with diverse predatory and defensive activities

Samantha A Nixon; Samuel D Robinson; Akello J Agwa; Andrew A Walker; Shivani Choudhary; Axel Touchard; Eivind A.B Undheim; Alan Robertson; Irina Vetter; Christina I Schroeder; Andrew C Kotze; Volker Herzig; Glenn F King

doi:10.1016/j.bcp.2021.114693

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Multipurpose peptides: The venoms of Amazonian stinging ants contain anthelmintic ponericins with diverse predatory and defensive activities

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Multipurpose peptides: The venoms of Amazonian stinging ants contain anthelmintic ponericins with diverse predatory and defensive activities

Samantha A Nixon, Samuel D Robinson, Akello J Agwa, Andrew A Walker, Shivani Choudhary, Axel Touchard, Eivind A.B Undheim, Alan Robertson, Irina Vetter, Christina I Schroeder, …

Biochemical Pharmacology, Vol.192, pp.1-16

2021

DOI: https://doi.org/10.1016/j.bcp.2021.114693

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Abstract

Ant

Anthelmintic

Antimicrobial

Pain

Ponericin

Venom peptide

In the face of increasing drug resistance, the development of new anthelmintics is critical for controlling nematodes that parasitise livestock. Although hymenopteran venom toxins have attracted attention for applications in agriculture and medicine, few studies have explored their potential as anthelmintics. Here we assessed hymenopteran venoms as a possible source of new anthelmintic compounds by screening a panel of ten hymenopteran venoms against Haemonchus contortus, a major pathogenic nematode of ruminants. Using bioassay-guided fractionation coupled with liquid chromatography-tandem mass spectrometry, we identified four novel anthelmintic peptides (ponericins) from the venom of the neotropical ant Neoponera commutata and the previously described ponericin M−PONTX−Na1b from Neoponera apicalis venom. These peptides inhibit H. contortus development with IC50 values of 2.8–5.6 μM. Circular dichroism spectropolarimetry indicated that the ponericins are unstructured in aqueous solution but adopt α-helical conformations in lipid mimetic environments. We show that the ponericins induce non-specific membrane perturbation, which confers broad-spectrum antimicrobial, insecticidal, cytotoxic, hemolytic, and algogenic activities, with activity across all assays typically correlated. We also show for the first time that ponericins induce spontaneous pain behaviour when injected in mice. We propose that the broad-spectrum activity of the ponericins enables them to play both a predatory and defensive role in neoponeran ants, consistent with their high abundance in venom. This study reveals a broader functionality for ponericins than previously assumed, and highlights both the opportunities and challenges in pursuing ant venom peptides as potential therapeutics.

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Title: Multipurpose peptides: The venoms of Amazonian stinging ants contain anthelmintic ponericins with diverse predatory and defensive activities
Authors: Samantha A Nixon (Author) - The University of Queensland
Samuel D Robinson (Author) - The University of Queensland
Akello J Agwa (Author) - The University of Queensland
Andrew A Walker (Author) - The University of Queensland
Shivani Choudhary (Author) - Iowa State University
Axel Touchard (Author) - Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Eivind A.B Undheim (Author) - The University of Queensland
Alan Robertson (Author) - Iowa State University
Irina Vetter (Author) - CSIRO Agriculture and Food (Australia)
Christina I Schroeder (Author) - The University of Queensland
Andrew C Kotze (Author) - CSIRO Agriculture and Food (Australia)
Volker Herzig (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
Glenn F King (Author) - The University of Queensland
Publication details: Biochemical Pharmacology, Vol.192, pp.1-16
Publisher: Elsevier Inc.
Date published: 2021
DOI: 10.1016/j.bcp.2021.114693
ISSN: 1873-2968; 0006-2952
Grants: Be(e) friendly venomous spiders! Novel biopesticides from arachnid venoms, FT190100482, Australian Research Council (Australia, Canberra) - ARC
ARC Centre of Excellence for Innovations in Peptide and Protein Science, CE200100012 , Australian Research Council (Australia, Canberra) - ARC
Venoms to drugs: translating venom peptides into human therapeutics, 1136889, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Nettles & toxic toupees: the molecular weaponry of venomous caterpillars, DP200102867, Australian Research Council (Australia, Canberra) - ARC
Gain from pain: new tools from venomous animals for exploring pain pathways, DP190103787, Australian Research Council (Australia, Canberra) - ARC
Understanding how toxins interact with lipid membranes and ion channels, 1080405, National Health and Medical Research Council (Australia, Canberra) - NHMRC
The potential of membranes – peptide engineering to modulate ion channels, FT160100055 , Australian Research Council (Australia, Canberra) - ARC
Grant note: This work was supported by the Westpac Bicentennial Foundation (Westpac Future Leaders Scholarship to S.A.N.),. E.A.B.U was supported by a Norwegian Research Council FRIPRO-YRT Fellowship no. 287462. A.T was supported by “Investissement d'Avenir” grant ANR-10-LABX-25-01from Agence Nationale de la Recherche and a “Fonds européen de développement regional” grant GY0013708. Collection of ant species in French Guiana have been subjected to a declarative procedure (NOR: TREL1734890A/27) for non-commercial use at the competent administrative authority, in accordance with Article L.412-7 of the French environmental code. A.J.A was supported by a UQ PhD Scholarship.
Organisation Unit: School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99579008202621
Output Type: Journal article

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Web Of Science research areas: Pharmacology & Pharmacy

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