Ant venoms contain vertebrate-selective pain-causing sodium channel toxins

Abstract

Stings of certain ant species (Hymenoptera: Formicidae) can cause intense, long-lasting nociception. Here we show that the major contributors to these symptoms are venom peptides that modulate the activity of voltage-gated sodium (NaV) channels, reducing their voltage threshold for activation and inhibiting channel inactivation. These peptide toxins are likely vertebrate-selective, consistent with a primarily defensive function. They emerged early in the Formicidae lineage and may have been a pivotal factor in the expansion of ants.

Adaptive trade-offs between vertebrate defense and insect predation drive ant venom evolution

“…Neurotoxic peptides are not exclusive to ants that rely on venom solely for predation. The venom of Pa. clavata is largely dominated by poneratoxin (family 62) (46), a pain-inducing neurotoxin that efficiently modulates vertebrate voltage-gated sodium (Na V ) channels while paralyzing insects only at very high doses (47). We showed that the venom of Pa. clavata also exhibits cytotoxicity, which is likely attributed to phospholipase A 2 (PLA 2 ), present in this venom at higher levels than in other ants.…”

“…In some lineages of ants, however, evolution may have favored neurotoxin-based venoms as the range of biological targets narrowed. A reasonable explanation for the prevalence of neurotoxic-based venoms in ants would be that cytotoxic peptides often act at high concentrations compared to neurotoxins (47), and are therefore likely to be associated with higher metabolic costs. Toxin innovation in the venoms of the Formicidae may therefore facilitate diversification of lifestyle and morphology, and ultimately contribute to speciation.…”