Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami

• DOI: 10.1038/srep29538
• Publication Date: 2016-07-07T09:14:06Z
• Authors: Volker Herzig; Maria Ikonomopoulou; Jennifer J. Smith; Sławomir Dziembor...; John Gilchrist; Lucia Kuhn-Nentwig; Fernanda Oliveira...; Luciano Andrade M...; Graham M. Nicholson; Frank Bosmans; Glenn F. King
• Keywords: Blattellidae/drug effects; Insecticides; Diptera/drug effects; Spiders/chemistry; Drug Evaluation, Preclinical; Spider Venoms; Voltage-Gated Sodium Channels; Article; NAV1.5 Voltage-Gated Sodium Channel; 03 medical and health sciences; Insect Proteins/antagonists & inhibitors; Voltage-Gated Sodium Channels/chemistry; Augacephalus ezendami; Periplaneta/drug effects; Recombinant Proteins/genetics; Animals; Periplaneta; Voltage-Gated Sodium Channel Blockers; Voltage-Gated Sodium Channel Blockers/pharmacology; 0303 health sciences; Insecticidal spider-venom peptides; Diptera; Spiders; Blattellidae; Sodium channel toxin; FoR multidisciplinary; Insecticides/chemistry; Recombinant Proteins; Lepidoptera; Drosophila melanogaster; Drosophila melanogaster/drug effects; Lepidoptera/drug effects; 1000 General; Spider Venoms/chemistry; NAV1.5 Voltage-Gated Sodium Channel/metabolism; Insect Proteins; Drug Evaluation, Preclinical/methods; Peptides; Peptides/genetics; Environmentally-friendly alternatives

AbstractThe inexorable decline in the armament of registered chemical insecticides has stimulated research into environmentally-friendly alternatives. Insecticidal spider-venom peptides are promising candidates for bioinsecticide development but it is challenging to find peptides that are specific for targeted pests. In the present study, we isolated an insecticidal peptide (Ae1a) from venom of the African spider Augacephalus ezendami (family Theraphosidae). Injection of Ae1a into sheep blowflies (Lucilia cuprina) induced rapid but reversible paralysis. In striking contrast, Ae1a was lethal to closely related fruit flies (Drosophila melanogaster) but induced no adverse effects in the recalcitrant lepidopteran pest Helicoverpa armigera. Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. We show that Ae1a interacts with the domain II voltage sensor and that sensitivity to the toxin is conferred by natural sequence variations in the S1–S2 loop of domain II. The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species.