Search Results (92)

Scorpion venoms contain a wide range of toxins that interact with a variety of target molecules (ion channels, receptors and enzymes) associated with synaptic transmission, action potential propagation, cardiac function, hemostasis and other physiological systems. Scorpion toxins are also active towards bacteria, viruses, fungi and parasites. Such interactions make scorpion toxins useful lead molecules for developing compounds with biotechnological and therapeutic applications, and as tools for cell biology. In addition, scorpion toxins act as insectotoxins, with promising applications as insecticides. This review describes the range of scorpion toxins and discusses their usefulness for the development of insecticides and therapeutic drugs. Full article

Lambda-cyhalothrin (LCY), a widely used pyrethroid insecticide, is toxic to bees—vital pollinators experiencing global declines; however, its molecular effects during early development remain poorly understood. We investigated the molecular mechanisms underlying chronic sublethal exposure to LCY in the larval and adult stages. Larvae were exposed to LCY (0.004 µg active ingredient/larva), with four groups examined: solvent-treated larvae group (SLG), solvent-treated adult group (SAG), LCY-treated larvae group (LLG), and LCY-treated adult group (LAG). We identified 1128 and 168 significantly altered genes in LLG vs. SLG and LAG vs. SAG, respectively, with 125 larval- and 25 adult-specific DEGs, indicating stage-dependent toxicity. LCY dysregulated processes such as cuticle formation, sulfur metabolism, oxidoreductase activity, and neuropeptide signaling in larvae, while adults exhibited altered redox balance, peptide receptor signaling, and monoamine transport. Neuroactive signaling disruptions were observed in both stages, with additional effects on motor function, amino acid metabolism, and glycolysis in larvae; whereas adults exhibited altered lipid biosynthesis and energy metabolism. Downregulated genes involved in chitin metabolism and antioxidant defenses in larvae suggested compromised exoskeletal integrity and increased vulnerability. Overall, our findings highlight the long-term molecular consequences of early-life exposure and emphasize the need for safer pesticide practices to protect pollinator health. Full article

Scorpion venom contains various insecticidal peptides. Previously, through transcriptome analysis of the venom gland of Liocheles australasiae, we identified precursor sequences of several peptides that share sequences similar to those acting on K⁺ channels. In this study, we chemically synthesized five of the peptides which were found in the venom and evaluated their insecticidal activity against crickets. This revealed that one of the peptides, named LaIT6, exhibited significant insecticidal activity without mammalian toxicity. To identify amino acid residues important for the insecticidal activity of LaIT6, nine analogs were synthesized mainly by substituting acidic, basic, and aromatic residues with alanine. This revealed that two basic residues and an aromatic residue in the C-terminal region are important for the activity. This characteristic of structure-activity relationships, known as a functional dyad, is commonly observed in peptides that act on K⁺ channels, suggesting that the action target of LaIT6 is K⁺ channels. As expected, LaIT6 showed significant inhibitory activity against insect K⁺ channels. Since no activity against human K⁺ channels was observed, we concluded that the selectivity of LaIT6 is determined by differences in the action on K⁺ channels between insects and mammals. Full article

With the sustainable increase in agricultural productivity, the need for safer, environmentally friendly pesticide alternatives is also growing. Metabolites of microorganisms (bacteria, fungi, actinomycetes) are emerging as potential bioactive compounds for integrated pest and disease management. These compounds comprise amino acids, carbohydrates, lipids, organic acids, phenolics, peptides, alkaloids, polyketides, and volatile organic compounds. The majority of them have insecticidal, fungicidal, and nematicidal activities. In this review, the classifications, biosynthetic pathways, and ecological functions of primary and secondary metabolites produced by microorganisms are discussed, including their mechanisms of action, ranging from competition to systemic acquired resistance in host plants. The article highlights the importance of microbial genera (viz., Bacillus sp., Pseudomonas sp., Trichoderma sp., Streptomyces sp., etc.) in making chemicals and biopesticides for crop defense. We present the possible applications of microbial biosynthesis strategies and synthetic biology tools in bioprocess development, covering recent innovations in formulation, delivery, and pathway engineering to enhance metabolite production. This review emphasizes the significance of microbial metabolites in improving the plant immunity, yield performance, reduction in pesticide application, and the sustainability of an ecological, sustainable, and resilient agricultural system. Full article

The hazelnut weevil larvae (Curculio dieckmanni) is a major pest of nut weevils, spending part of its life cycle in the soil and causing significant damage to hazelnut crops. Moreover, its concealed feeding behavior complicates effective control with chemical insecticides. The entomopathogenic nematode Steinernema carpocapsae, which efficiently kills weevil larvae, offers a promising biological control agent. To investigate the molecular responses of hazelnut weevil larvae to nematode infection, we employed integrated transcriptomic and proteomic analyses following infection by S. carpocapsae. Our results revealed substantial alterations in gene expression, particularly the upregulation of immune-related transcripts such as antimicrobial peptides (AMPs) and stress-responsive proteins like heat shock protein 70 (HSP70). Furthermore, significant metabolic reprogramming occurred, marked by the downregulation of carbohydrate metabolic pathways and activation of energy conservation mechanisms. Although we observed an overall correlation between mRNA and protein expression levels, notable discrepancies highlighted the critical roles of post-transcriptional and post-translational regulatory processes. Collectively, these findings advance our understanding of the molecular interaction between insect hosts and pathogenic nematodes and contribute valuable knowledge for enhancing the effectiveness of EPN-based pest management strategies. Full article

The South China Sea is rich in cone snail resources, known for producing conotoxins with diverse biological activities such as analgesic, anticancer, and insecticidal effects. In this study, five vermivorous cone snail samples were collected from the South China Sea and their crude venom was extracted to investigate the variations in venom components and activities, aiming to identify highly active samples for further research. Cluster analysis using reverse-phase high-performance liquid chromatography (RP-HPLC) fingerprints and mitochondrial cytochrome c oxidase I (COI) gene sequences revealed that the diversity of venom components across different conotoxin species is genetically correlated. Activity assays demonstrated that all five cone snail venoms exhibited lethal effects on insects and zebrafish. Notably, the crude venom of Conus quercinus showed the highest insecticidal activity with an LD₅₀ of 0.6 μg/mg, while C. tessellatus venom exhibited the most potent zebrafish lethality with an LD₅₀ of 0.2 μg/mg. Furthermore, the crude venom from four cone snail species demonstrated toxicity against ovarian cancer cells, and only C. caracteristicu venom displayed significant analgesic activity. This study systematically identifies cone snail samples with promising insecticidal, anticancer, and analgesic properties, paving the way for the development and utilization of cone snail resources from the South China Sea and offering a novel approach for advancing marine peptide drug research. Full article

Rotenone, a naturally occurring compound derived from the roots of tropical plants, is used as a broad-spectrum insecticide, piscicide, and pesticide. It is a classical, high-affinity mitochondrial complex I inhibitor that causes not only oxidative stress, α-synuclein phosphorylation, DJ-1 (Parkinson’s disease protein 7) modifications, and inhibition of the ubiquitin-proteasome system but it is also widely considered an environmental contributor to Parkinson’s disease (PD). While prodromal symptoms, such as loss of smell, constipation, sleep disorder, anxiety/depression, and the loss of dopaminergic neurons in the substantia nigra of rotenone-treated animals, have been reported, alterations of metabolic hormones and hyperinsulinemia remain largely unknown and need to be investigated. Whether rotenone and its effect on metabolic peptides could be utilized as a biomarker for its toxic metabolic effects, which can cause long-term detrimental effects and ultimately lead to obesity, hyperinsulinemia, inflammation, and possibly gut–brain axis dysfunction, remains unclear. Here, we show that rotenone disrupts metabolic homeostasis, altering hormonal peptides and promoting infiltration of inflammatory T cells. Specifically, our results indicate a significant decrease in glucagon-like peptide-1 (GLP-1), C-peptide, and amylin. Interestingly, levels of several hormonal peptides related to hyperinsulinemia, such as insulin, leptin, pancreatic peptide (PP), peptide YY (PYY), and gastric inhibitory polypeptide (GIP), were significantly upregulated. Administration of rotenone to rats also increased body weight and activated macrophages and inflammatory T cells. These data strongly suggest that rotenone disrupts metabolic homeostasis, leading to obesity and hyperinsulinemia. The potential implications of these findings are vast, given that monitoring these markers in the blood could not only provide a crucial tool for assessing the extent of exposure and its relevance to obesity and inflammation but could also open new avenues for future research and potential therapeutic strategies. Full article

Scorpion venom contains various bioactive peptides, many of which exhibit insecticidal activity. The majority of these peptides have a cystine-stabilized α-helix/β-sheet (CSαβ) motif. In addition to these peptides, scorpion venom also contains those with a cystine-stabilized α-helix/α-helix (CSαα) motif, which are known as κ-KTx peptides. Some of these peptides show weak inhibitory activity on mammal potassium channels, but, in many cases, their biological activity remained unknown. In this study, with the aim of discovering novel insecticidal peptides, we synthesized five peptides, which were predicted to adopt a CSαα motif, identified from the venom of the scorpion Liocheles australasiae, and measured their insecticidal activity. As a result, one of the peptides, named LaIT5, exhibited significant insecticidal activity. To the best of our knowledge, this is the first report of insecticidal peptides with a CSαα motif. Furthermore, we synthesized its analogs based on sequence comparisons with other inactive CSαα-motif peptides to identify amino acid residues important for its insecticidal activity. The results indicate that two consecutive His residues at the central region of LaIT5 are particularly important for the activity. Since LaIT5 did not show any toxicity against mice, it was concluded that its action is selective for insects. Full article

ABC toxin complexes are a class of protein toxin translocases comprised of a multimeric assembly of protein subunits. Each subunit displays a unique composition, contributing to the formation of a syringe-like nano-machine with natural cargo carrying, targeting, and translocation capabilities. Many of these toxins are insecticidal, drawing increasing interest in agriculture for use as biological pesticides. The A subunit (TcA) is the largest subunit of the complex and contains domains associated with membrane permeation and targeting. The B and C subunits, TcB and TcC, respectively, package into a cocoon-like structure that contains a toxic peptide and are coupled to TcA to form a continuous channel upon final assembly. In this review, we outline the current understanding and gaps in the knowledge pertaining to ABC toxins, highlighting seven published structures of TcAs and how these structures have led to a better understanding of the mechanism of host tropism and toxin translocation. We also highlight similarities and differences between homologues that contribute to variations in host specificity and conformational change. Lastly, we review the biotechnological potential of ABC toxins as both pesticides and cargo-carrying shuttles that enable the transport of peptides into cells. Full article

Entomopathogenic bacteria, classified into the genus Xenorhabdus, exhibit a dual lifestyle as mutualistic symbionts to Steinernema nematodes and as pathogens to a broad range of insects. Bacterial virulence depends on toxin proteins that induce toxemia and various immunosuppressive secondary metabolites that cause septicemia. Particularly, the immunosuppressive properties of Xenorhabdus bacteria determine the variability of their insecticidal activities. This study explored the role of peptide metabolites in virulence and its variation among six bacterial strains across three species: X. nematophila, X. bovienii, and X. hominickii. Initially, their virulence significantly varied against a susceptible lepidopteran host, Maruca vitrata, but showed less variation against a tolerant coleopteran host, Tenebrio molitor, with high median lethal bacterial doses. In M. vitrata, virulence was strongly correlated with bacterial growth rate and inhibitory activity against phospholipase A₂. Secondly, the six strains differed in the compositions of their secreted secondary metabolites, analyzed by GC-MS following ethyl acetate extraction. Notably, there was significant variation in the production of di- or tetra-peptides. Highly virulent strains commonly produced the cyclic Pro-Phe (cPF). Thirdly, the expression of non-ribosomal peptide synthetase (NRPS) genes varied greatly among the strains. NRPS genes were minimally expressed in the tolerant T. molitor and highly expressed in the susceptible M. vitrata. In M. vitrata, specific NRPS genes were markedly expressed in the virulent strains. Finally, cPF demonstrated potent immunosuppressive activity against the cellular and humoral responses of M. vitrata. The addition of cPF significantly enhanced the virulence against the tolerant T. molitor. These findings suggest that immunosuppression is necessary for the pathogenicity of Xenorhabdus bacteria, wherein NRPS products play a critical role in suppressing immune-associated factors in target insects. Full article

HxTx-Hv1h, a neurotoxic peptide derived from spider venom, has been developed for use in commercial biopesticide formulations. Cell Penetrating Peptides (CPPs) are short peptides that facilitate the translocation of various biomolecules across cellular membranes. Here, we evaluated the aphidicidal efficacy of a conjugated peptide, HxTx-Hv1h/CPP-1838, created by fusing HxTx-Hv1h with CPP-1838. Additionally, we aimed to establish a robust recombinant expression system for HxTx-Hv1h/CPP-1838. We successfully achieved the secretory production of HxTx-Hv1h, its fusion with Galanthus nivalis agglutinin (GNA) forming HxTx-Hv1h/GNA and HxTx-Hv1h/CPP-1838 in yeast. Purified HxTx-Hv1h exhibited contact toxicity against Megoura crassicauda, with a 48 h median lethal concentration (LC₅₀) of 860.5 μg/mL. Fusion with GNA or CPP-1838 significantly enhanced its aphidicidal potency, reducing the LC₅₀ to 683.5 μg/mL and 465.2 μg/mL, respectively. The aphidicidal efficacy was further improved with the addition of surfactant, decreasing the LC₅₀ of HxTx-Hv1h/CPP-1838 to 66.7 μg/mL—over four times lower compared to HxTx-Hv1h alone. Furthermore, we engineered HxTx-Hv1h/CPP-1838 multi-copy expression vectors utilizing the BglBrick assembly method and achieved high-level recombinant production in laboratory-scale fermentation. This study is the first to document a CPP fusion strategy that enhances the transdermal aphidicidal activity of a natural toxin like HxTx-Hv1h and opens up the possibility of exploring the recombinant production of HxTx-Hv1h/CPP-1838 for potential applications. Full article

The escalating resistance of agricultural pests to chemical insecticides necessitates the development of novel, efficient, and safe biological insecticides. Conus quercinus, a vermivorous cone snail, yields a crude venom rich in peptides for marine worm predation. This study screened six α-conotoxins with insecticidal potential from a previously constructed transcriptome database of C. quercinus, characterized by two disulfide bonds. These conotoxins were derived via solid-phase peptide synthesis (SPPS) and folded using two-step iodine oxidation for further insecticidal activity validation, such as CCK-8 assay and insect bioassay. The final results confirmed the insecticidal activities of the six α-conotoxins, with Qc1.15 and Qc1.18 exhibiting high insecticidal activity. In addition, structural analysis via homology modeling and functional insights from molecular docking offer a preliminary look into their potential insecticidal mechanisms. In summary, this study provides essential references and foundations for developing novel insecticides. Full article

An insect neuroactive helix ring peptide called U₁₁-MYRTX-Tb1a (abbreviated as U₁₁) from the venom of the ant, Tetramorium bicarinatum. U₁₁ is a 34-amino-acid peptide that is claimed to be one of the most paralytic peptides ever reported from ant venoms acting against blowflies and honeybees. The peptide features a compact triangular ring helix structure stabilized by a single disulfide bond, which is a unique three-dimensional scaffold among animal venoms. Pharmacological assays using Drosophila S2 cells have demonstrated that U₁₁ is not cytotoxic but instead suggest that it may modulate potassium channels via the presence of a functional dyad. In our work described here, we have tested this hypothesis by investigating the action of synthetically made U₁₁ on a wide array of voltage-gated K and Na channels since it is well known that these channels play a crucial role in the phenomenon of paralysis. Using the Xenopus laevis oocyte heterologous expression system and voltage clamp, our results have not shown any modulatory effect of 1 μM U₁₁ on the activity of Kv1.1, Kv1.3, Kv1.4, Kv1.5, Shaker IR, Kv4.2, Kv7.1, Kv10.1, Kv11.1 and KQT1, nor on DmNav and BgNav. Instead, 10 μM U₁₁ caused a quick and irreversible cytolytic effect, identical to the cytotoxic effect caused by Apis mellifera venom, which indicates that U₁₁ can act as a pore-forming peptide. Interestingly, the paralytic dose (PD₅₀) on blowflies and honeybees corresponds with the concentration at which U₁₁ displays clear pore-forming activity. In conclusion, our results indicate that the insecticidal and paralytic effects caused by U₁₁ may be explained by the putative pore formation of the peptide. Full article

Currently, insecticides that target nicotinic acetylcholine receptors (nAChR) are widely used. Studies on the sublethal effects of insecticides have found that they can affect the amount of virus in insects. The mechanism by which insecticides affect insect virus load remain unclear. Here, we show that nAChR targeting insecticide can affect viral replication through the immune deficiency (IMD) pathway. We demonstrate that a low dose of spinosad (6.8 ng/mL), acting as an antagonist to Drosophila melanogaster nicotinic acetylcholine receptor α6 (Dα6), significantly elevates Drosophila melanogaster sigmavirus (DMelSV) virus titers in adults of Drosophila melanogaster. Conversely, a high dose of spinosad (50 ng/mL), acting as an agonist to Dα6, substantially decreases viral load. This bidirectional regulation of virus levels is absent in Dα6-knockout flies, signifying the specificity of spinosad’s action through Dα6. Furthermore, the knockdown of Dα6 results in decreased expression of genes in the IMD pathway, including dredd, imd, relish, and downstream antimicrobial peptide genes AttA and AttB, indicating a reduced innate immune response. Subsequent investigations reveal no significant difference in viral titers between relish mutant flies and Dα6-relish double mutants, suggesting that the IMD pathway’s role in antiviral defense is dependent on Dα6. Collectively, our findings shed light on the intricate interplay between nAChR signaling and the IMD pathway in mediating antiviral immunity, highlighting the potential for nAChR-targeting compounds to inadvertently influence viral dynamics in insect hosts. This knowledge may inform the development of integrated pest management strategies that consider the broader ecological impact of insecticide use. Full article

The genus Bruguiera, a member of the Rhizophoraceae family, is predominantly found in coastal areas as a mangrove plant, boasting a rich and diverse community of endophytes. This review systematically compiled approximately 496 compounds derived from both the Bruguiera genus and its associated endophytes, including 152 terpenoids, 17 steroids, 16 sulfides, 44 alkaloids and peptides, 66 quinones, 68 polyketides, 19 flavonoids, 38 phenylpropanoids, 54 aromatic compounds, and 22 other compounds. Among these, 201 compounds exhibited a spectrum of activities, including cytotoxicity, antimicrobial, antioxidant, anti-inflammatory, antiviral, antidiabetic, insecticidal and mosquito repellent, and enzyme inhibitory properties, etc. These findings provided promising lead compounds for drug discovery. Certain similar or identical compounds were found to be simultaneously present in both Bruguiera plants and their endophytes, and the phenomenon of their interaction relationship was discussed. Full article