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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/?-TRTX-Mb1a and -Mb1b, from venom of the African tarantula Monocentropus balfouri. Recombinant µ/?-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.

SUBMITTER: Smith JJ

PROVIDER: S-EPMC5450703 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Smith Jennifer J JJ Herzig Volker V Ikonomopoulou Maria P MP Dziemborowicz Sławomir S Bosmans Frank F Bosmans Frank F Nicholson Graham M GM King Glenn F GF

Toxins 20170505 5

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 -M ...[more]

PMID: 28475112

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Project description:Baculoviruses are the most studied insect viruses in the world and are used for biological control of agricultural and forest insect pests. They are also used as versatile vectors for expression of heterologous proteins. One of the major problems of their use as biopesticides is their slow speed to kill insects. Thus, to address this shortcoming, insect-specific neurotoxins from arachnids have been introduced into the baculovirus genome solely aiming to improve its virulence. In this work, an insecticide-like toxin gene was obtained from a cDNA derived from the venom glands of the theraphosid spider Brachypelma albiceps. The mature form of the peptide toxin (called Ba3) has a high content of basic amino acid residues, potential for three possible disulfide bonds, and a predicted three-stranded β-sheetDifferent constructions of the gene were engineered for recombinant baculovirus Autographa californica multiple nuclepolyhedrovirus (AcMNPV) expression. Five different forms of Ba3 were assessed; (1) the full-length sequence, (2) the pro-peptide and mature region, (3) only the mature region, and the mature region fused to an (4) insect or a (5) virus-derived signal peptide were inserted separately into the genome of the baculovirus. All the recombinant viruses induced cell death by necrosis earlier in infection relative to a control virus lacking the toxin gene. However, the recombinant virus containing the mature portion of the toxin gene induced a faster cell death than the other recombinants. We found that the toxin construct with the signal peptide and/or pro-peptide regions delayed the necrosis phenotype. When infected cells were subjected to ultrastructural analysis, the cells showed loss of plasma membrane integrity and structural changes in mitochondria before death. Our results suggest this use of baculovirus is a potential tool to help understand or to identify the effect of insect-specific toxic peptides when produced during infection of insect cells.

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

Publications

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

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