Abstract
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.
Highlights
The Australian jack jumper ant, Myrmecia pilosula, is a species of bull ant within the M. pilosula species complex, endemic to the temperate Eastern regions of Australia [1]
Most animal venoms have evolved to assist with predation, they are used for a variety of other roles including defense against predators, intraspecific competition, conspecific communication, chemical detoxification
Several venom-derived antimicrobial peptides are active against a range of human parasites, including cupiennin 1a from the wandering spider Cupiennius salei, which is active against both trypanosomes and malaria parasites [15,16], the antimalarial peptides meucin-24 and 25 from the scorpion Mesobuthus eupeus [17], and the antitrypanosomal dinoponeratoxins from the giant ant Dinoponera quadriceps [18]
Summary
The Australian jack jumper ant, Myrmecia pilosula, is a species of bull ant within the M. pilosula species complex, endemic to the temperate Eastern regions of Australia [1]. We hypothesized that Mp1a, as a membrane-disrupting peptide and the major venom component, might serve both defensive (i.e., pain-inducing) and predatory (i.e., insecticidal) roles. Mp1a and synthetic analogues have already been shown to have antibiotic activity, including against the opportunistic human pathogen Acinetobacter baumannii [5]. Several venom-derived antimicrobial peptides are active against a range of human parasites, including cupiennin 1a from the wandering spider Cupiennius salei, which is active against both trypanosomes and malaria parasites [15,16], the antimalarial peptides meucin-24 and 25 from the scorpion Mesobuthus eupeus [17], and the antitrypanosomal dinoponeratoxins from the giant ant Dinoponera quadriceps [18]. Activity relationships for Mp1a in relation to their insecticidal, cytotoxic, antiparasitic and algogenic properties to assess their selectivity and potential as human or veterinary therapeutics
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