Insect-Active Toxins with Promiscuous Pharmacology from the African Theraphosid Spider Monocentropus balfouri

Abstract

Many chemical insecticides are becoming less efficacious due to rising resistance in pest species, which has created much interest in the development of new, eco-friendly bioinsecticides. Since insects are the primary prey of most spiders, their venoms are a rich source of insect-active peptides that can be used as leads for new bioinsecticides or as tools to study molecular receptors that are insecticidal targets. In the present study, we isolated two insecticidal peptides, µ/ω-TRTX-Mb1a and -Mb1b, from venom of the African tarantula Monocentropus balfouri. Recombinant µ/ω-TRTX-Mb1a and -Mb1b paralyzed both Lucilia cuprina (Australian sheep blowfly) and Musca domestica (housefly), but neither peptide affected larvae of Helicoverpa armigera (cotton bollworms). Both peptides inhibited currents mediated by voltage-gated sodium (NaV) and calcium channels in Periplaneta americana (American cockroach) dorsal unpaired median neurons, and they also inhibited the cloned Blattella germanica (German cockroach) NaV channel (BgNaV1). An additional effect seen only with Mb1a on BgNaV1 was a delay in fast inactivation. Comparison of the NaV channel sequences of the tested insect species revealed that variations in the S1–S2 loops in the voltage sensor domains might underlie the differences in activity between different phyla.

A subfraction obtained from the venom of the tarantula Poecilotheria regalis contains inhibitor cystine knot peptides and induces relaxation of rat aorta by inhibiting L-type voltage-gated calcium channels

“…Since the vasodilatory effect of PrFr-I was not affected by the presence of TEA nor PrFr-I affected amplitude or currents elicited by K v 10.1, these results suggest that PrFr-I contains ICK peptide toxins capable of inhibiting Ca v channels, thereby inducing relaxation of rat aortic rings by suppressing Ca 2+ influx to vascular smooth muscle. Admittedly, promiscuous ICK peptide toxins can affect Na v and Ca v channels as a synergistic strategy to modulate neuronal transmission ( Klint et al, 2014 ; Smith et al, 2017 ). Therefore, PrFr-I may contain promiscuous ICK peptide toxins capable of modulating L-type Ca v channels and Na v 1.7.…”

Versatile spider venom peptides and their medical and agricultural applications

“…As indicated in table 5, not all novel ISPs immediately induced lethality in the target insects. Some ISPs caused completely reversible paralysis (Herzig et al, 2016;Smith et al, 2017;Sousa et al, 2017), while others caused a long-lasting paralysis that eventually resulted in death by starvation (Ikonomopoulou et al, 2016;Matsubara et al, 2017). And these ISP-induced effects did not only vary between ISPs, but also within ISPs tested across a range of target insect species.…”

GiTx1(β/κ-theraphotoxin-Gi1a), a novel toxin from the venom of Brazilian tarantula Grammostola iheringi (Mygalomorphae, Theraphosidae): Isolation, structural assessments and activity on voltage-gated ion channels

“…For instance, Hainan toxins showed high affinity for Kv channels and low affinity for Cav channels, whereas the opposite was observed for ω-TRTX-Gr1a (GsTxSIA) [32]. Likewise, several works have been reporting the promiscuous activity of tarantula's toxins [33][34][35][36]. As consequence of the promiscuity displayed by these toxins, its functional prediction becomes a difficult task.…”