Animal Toxins: Biodiscovery, Mechanistic Insights and Translational Potential

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 15576

Special Issue Editors


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Guest Editor
Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Animal Venomics Research Group, Ohlebergsweg.12, 35392 Gießen, Germany
Interests: animal venoms; animal poisons; venomics; biodiscovery; biotechnology

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Guest Editor
Center of Allergy and Environment (ZAUM), Technical University of Munich, Faculty of Medicine and Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Munich, Germany
Interests: hymenoptera venom; venom allergy; allergy; immunological mechanisms; T cell response; B cell response; antibodies; immunological tolerance; allergen; venom proteomics; biochemical protein characterization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Animal toxins are evolutionarily refined molecular weapons with tremendous translational potential. However, only a subset of all venomous and poisonous animals has been investigated thus far and, accordingly, the vast majority of biomolecules present in these remain to be discovered. For many toxins, the biological functions, modes of action and structural constraints (including the effects of post-translational modifications) are yet to be determined. Our ability to bridge these important knowledge gaps has recently been enhanced by diverse methodological breakthroughs, particularly in bioanalytics, biotechnology and bioassays.

This Special Issue aims to serve as a collection of excellent contributions on animal toxin biodiscovery, function and applications. It seeks to pioneer biodiscovery across the animal kingdom, providing important insights into the bioactivities and mechanistic foundations of hitherto understudied compounds and promoting their translational use. It therefore welcomes experimental studies and review articles that employ state-of-the-art technologies (e.g., genomics, proteomics or metabolomics) in uncovering novel biomolecules from venoms and poisons. It will also feature works that investigate the mode of action, structure–function relationships and effects of chemical modification on toxin bioactivity as well as studies that explore the translational potential of animal toxins in biomedicine, industrial production and agronomy.

Dr. Tim Lüddecke
Dr. Simon Blank
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • venomics
  • bioprospecting
  • mode of action
  • structure–function
  • molecular targets
  • biomedicine
  • agronomy

Published Papers (9 papers)

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Editorial

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3 pages, 206 KiB  
Editorial
Animal Toxins: Biodiscovery, Mechanistic Insights and Translational Potential
by Tim Lüddecke and Simon Blank
Toxins 2024, 16(3), 130; https://doi.org/10.3390/toxins16030130 - 01 Mar 2024
Viewed by 908
Abstract
Nature abounds with an unprecedented diversity of biomolecular innovation [...] Full article

Research

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13 pages, 3958 KiB  
Article
Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells
by Reema M. Alzeer, Khaled S. Al-Hadyan, Najla M. Al-Harbi, Sara S. Bin Judia, Rafa S. Almeer and Ghazi A. Alsbeih
Toxins 2023, 15(12), 701; https://doi.org/10.3390/toxins15120701 - 15 Dec 2023
Viewed by 1323
Abstract
Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant “Myrmecia pilosula”, as a cytotoxic and radiosensitizing agent in [...] Read more.
Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant “Myrmecia pilosula”, as a cytotoxic and radiosensitizing agent in MCF-7 and MDA-MB-231 breast cancer (BC) cell lines. Pilosulin-3’s cytotoxicity was evaluated across a wide range of concentrations using a proliferation assay. Cell cycle progression and apoptosis were examined at the inhibitory concentration 25% (IC25) and IC50 of Pilosulin-3, both with and without a 4Gy X-ray irradiation dose. Radiosensitivity was assessed at IC25 using the clonogenic survival assay. The study revealed that Pilosulin-3 exerted a concentration-dependent cytotoxic effect, with IC25 and IC50 values of 0.01 and 0.5 µM, respectively. In silico screening indicated high selectivity of Pilosulin-3 peptide, which was predicted to be the most likely anticancer agent (PROB = 0.997) with low hemolytic activity (PROP = 0.176). Although Pilosulin-3 exhibited a significant (p < 0.05) G2/M cell cycle arrest in combination with radiation, there was no discernible effect on apoptosis induction or cell survival following irradiation. In conclusion, Pilosulin-3 proved to be cytotoxic to BC cells and induced a cytostatic effect (G2/M arrest) when combined with radiation. However, it did not enhance the efficacy of cell killing by irradiation. While it holds potential as a cytotoxic agent in breast cancer treatment, its application as a radiosensitizer does not find support in these results. Full article
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14 pages, 2338 KiB  
Article
Two Novel Mosquitocidal Peptides Isolated from the Venom of the Bahia Scarlet Tarantula (Lasiodora klugi)
by Jamila Ahmed, Andrew A. Walker, Hugo D. Perdomo, Shaodong Guo, Samantha A. Nixon, Irina Vetter, Hilary I. Okoh, Dalhatu M. Shehu, Mohammed N. Shuaibu, Iliya S. Ndams, Glenn F. King and Volker Herzig
Toxins 2023, 15(7), 418; https://doi.org/10.3390/toxins15070418 - 27 Jun 2023
Viewed by 1755
Abstract
Effective control of diseases transmitted by Aedes aegypti is primarily achieved through vector control by chemical insecticides. However, the emergence of insecticide resistance in A. aegypti undermines current control efforts. Arachnid venoms are rich in toxins with activity against dipteran insects and we therefore [...] Read more.
Effective control of diseases transmitted by Aedes aegypti is primarily achieved through vector control by chemical insecticides. However, the emergence of insecticide resistance in A. aegypti undermines current control efforts. Arachnid venoms are rich in toxins with activity against dipteran insects and we therefore employed a panel of 41 spider and 9 scorpion venoms to screen for mosquitocidal toxins. Using an assay-guided fractionation approach, we isolated two peptides from the venom of the tarantula Lasiodora klugi with activity against adult A. aegypti. The isolated peptides were named U-TRTX-Lk1a and U-TRTX-Lk2a and comprised 41 and 49 residues with monoisotopic masses of 4687.02 Da and 5718.88 Da, respectively. U-TRTX-Lk1a exhibited an LD50 of 38.3 pmol/g when injected into A. aegypti and its modeled structure conformed to the inhibitor cystine knot motif. U-TRTX-Lk2a has an LD50 of 45.4 pmol/g against adult A. aegypti and its predicted structure conforms to the disulfide-directed β-hairpin motif. These spider-venom peptides represent potential leads for the development of novel control agents for A. aegypti. Full article
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22 pages, 5156 KiB  
Article
Multi-Omic Identification of Venom Proteins Collected from Artificial Hosts of a Parasitoid Wasp
by Kaili Yu, Jin Chen, Xue Bai, Shijiao Xiong, Xinhai Ye, Yi Yang, Hongwei Yao, Fang Wang, Qi Fang, Qisheng Song and Gongyin Ye
Toxins 2023, 15(6), 377; https://doi.org/10.3390/toxins15060377 - 03 Jun 2023
Viewed by 1616
Abstract
Habrobracon hebetor is a parasitoid wasp capable of infesting many lepidopteran larvae. It uses venom proteins to immobilize host larvae and prevent host larval development, thus playing an important role in the biocontrol of lepidopteran pests. To identify and characterize its venom proteins, [...] Read more.
Habrobracon hebetor is a parasitoid wasp capable of infesting many lepidopteran larvae. It uses venom proteins to immobilize host larvae and prevent host larval development, thus playing an important role in the biocontrol of lepidopteran pests. To identify and characterize its venom proteins, we developed a novel venom collection method using an artificial host (ACV), i.e., encapsulated amino acid solution in paraffin membrane, allowing parasitoid wasps to inject venom. We performed protein full mass spectrometry analysis of putative venom proteins collected from ACV and venom reservoirs (VRs) (control). To verify the accuracy of proteomic data, we also collected venom glands (VGs), Dufour’s glands (DGs) and ovaries (OVs), and performed transcriptome analysis. In this paper, we identified 204 proteins in ACV via proteomic analysis; compared ACV putative venom proteins with those identified in VG, VR, and DG via proteome and transcriptome approaches; and verified a set of them using quantitative real-time polymerase chain reaction. Finally, 201 ACV proteins were identified as potential venom proteins. In addition, we screened 152 and 148 putative venom proteins identified in the VG transcriptome and the VR proteome against those in ACV, and found only 26 and 25 putative venom proteins, respectively, were overlapped with those in ACV. Altogether, our data suggest proteome analysis of ACV in combination with proteome–transcriptome analysis of other organs/tissues will provide the most comprehensive identification of true venom proteins in parasitoid wasps. Full article
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16 pages, 3120 KiB  
Article
Functional Profiling of the A-Family of Venom Peptides from the Wolf Spider Lycosa shansia
by Tim Lüddecke, Ludwig Dersch, Lennart Schulte, Sabine Hurka, Anne Paas, Markus Oberpaul, Johanna Eichberg, Kornelia Hardes, Sven Klimpel and Andreas Vilcinskas
Toxins 2023, 15(5), 303; https://doi.org/10.3390/toxins15050303 - 22 Apr 2023
Cited by 1 | Viewed by 1761
Abstract
The venoms of spiders from the RTA (retro-lateral tibia apophysis) clade contain diverse short linear peptides (SLPs) that offer a rich source of therapeutic candidates. Many of these peptides have insecticidal, antimicrobial and/or cytolytic activities, but their biological functions are unclear. Here, we [...] Read more.
The venoms of spiders from the RTA (retro-lateral tibia apophysis) clade contain diverse short linear peptides (SLPs) that offer a rich source of therapeutic candidates. Many of these peptides have insecticidal, antimicrobial and/or cytolytic activities, but their biological functions are unclear. Here, we explore the bioactivity of all known members of the A-family of SLPs previously identified in the venom of the Chinese wolf spider (Lycosa shansia). Our broad approach included an in silico analysis of physicochemical properties and bioactivity profiling for cytotoxic, antiviral, insecticidal and antibacterial activities. We found that most members of the A-family can form α-helices and resemble the antibacterial peptides found in frog poison. The peptides we tested showed no cytotoxic, antiviral or insecticidal activities but were able to reduce the growth of bacteria, including clinically relevant strains of Staphylococcus epidermidis and Listeria monocytogenes. The absence of insecticidal activity may suggest that these peptides have no role in prey capture, but their antibacterial activity may help to defend the venom gland against infection. Full article
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18 pages, 4204 KiB  
Article
An Assassin’s Secret: Multifunctional Cytotoxic Compounds in the Predation Venom of the Assassin Bug Psytalla horrida (Reduviidae, Hemiptera)
by Maike Laura Fischer, Benjamin Fabian, Yannick Pauchet, Natalie Wielsch, Silke Sachse, Andreas Vilcinskas and Heiko Vogel
Toxins 2023, 15(4), 302; https://doi.org/10.3390/toxins15040302 - 20 Apr 2023
Cited by 1 | Viewed by 2401
Abstract
Predatory assassin bugs produce venomous saliva that enables them to overwhelm, kill, and pre-digest large prey animals. Venom from the posterior main gland (PMG) of the African assassin bug Psytalla horrida has strong cytotoxic effects, but the responsible compounds are yet unknown. Using [...] Read more.
Predatory assassin bugs produce venomous saliva that enables them to overwhelm, kill, and pre-digest large prey animals. Venom from the posterior main gland (PMG) of the African assassin bug Psytalla horrida has strong cytotoxic effects, but the responsible compounds are yet unknown. Using cation-exchange chromatography, we fractionated PMG extracts from P. horrida and screened the fractions for toxicity. Two venom fractions strongly affected insect cell viability, bacterial growth, erythrocyte integrity, and intracellular calcium levels in Drosophila melanogaster olfactory sensory neurons. LC-MS/MS analysis revealed that both fractions contained gelsolin, redulysins, S1 family peptidases, and proteins from the uncharacterized venom protein family 2. Synthetic peptides representing the putative lytic domain of redulysins had strong antimicrobial activity against Escherichia coli and/or Bacillus subtilis but only weak toxicity towards insect or mammalian cells, indicating a primary role in preventing the intake of microbial pathogens. In contrast, a recombinant venom protein family 2 protein significantly reduced insect cell viability but exhibited no antibacterial or hemolytic activity, suggesting that it plays a role in prey overwhelming and killing. The results of our study show that P. horrida secretes multiple cytotoxic compounds targeting different organisms to facilitate predation and antimicrobial defense. Full article
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14 pages, 18643 KiB  
Article
Pathophysiological and Clinical Significance of Crotalus durissus cascavella Venom-Induced Pulmonary Impairment in a Murine Model
by Ricardo G. Figueiredo, Marcos Lázaro da Silva Guerreiro, Elen Azevedo, Mateus Souza de Moura, Soraya Castro Trindade, José de Bessa, Jr. and Ilka Biondi
Toxins 2023, 15(4), 282; https://doi.org/10.3390/toxins15040282 - 14 Apr 2023
Viewed by 1560
Abstract
Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 [...] Read more.
Crotalus venom has broad biological activity, including neurotoxic, myotoxic, hematologic, and cytotoxic compounds that induce severe systemic repercussions. We evaluated the pathophysiological and clinical significance of Crotalus durissus cascavella (Cdc) venom-induced pulmonary impairment in mice. We conducted a randomized experimental study, involving 72 animals intraperitoneally inoculated with saline solution in the control group (CG), as well as venom in the experimental group (EG). The animals were euthanized at predetermined intervals (1 h, 3 h, 6 h, 12 h, 24 h, and 48 h), and lung fragments were collected for H&E and Masson histological analysis. The CG did not present inflammatory alterations in pulmonary parenchyma. In the EG, interstitial and alveolar swelling, necrosis, septal losses followed by alveolar distensions, and areas of atelectasis in the pulmonary parenchyma were observed after three hours. The EG morphometric analysis presented pulmonary inflammatory infiltrates at all time intervals, being more significant at three and six (p = 0.035) and six and 12 h (p = 0.006). The necrosis zones were significant at intervals of one and 24 h (p = 0.001), one and 48 h (p = 0.001), and three and 48 h (p = 0.035). Crotalus durissus cascavella venom induces a diffuse, heterogeneous, and acute inflammatory injury in the pulmonary parenchyma, with potential clinical implications for respiratory mechanics and gas exchange. The early recognition and prompt treatment of this condition are essential to prevent further lung injury and to improve outcomes. Full article
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14 pages, 2021 KiB  
Article
Bioactivity Profiling of In Silico Predicted Linear Toxins from the Ants Myrmica rubra and Myrmica ruginodis
by Sabine Hurka, Tim Lüddecke, Anne Paas, Ludwig Dersch, Lennart Schulte, Johanna Eichberg, Kornelia Hardes, Karina Brinkrolf and Andreas Vilcinskas
Toxins 2022, 14(12), 846; https://doi.org/10.3390/toxins14120846 - 02 Dec 2022
Cited by 3 | Viewed by 2120
Abstract
The venoms of ants (Formicidae) are a promising source of novel bioactive molecules with potential for clinical and agricultural applications. However, despite the rich diversity of ant species, only a fraction of this vast resource has been thoroughly examined in bioprospecting programs. Previous [...] Read more.
The venoms of ants (Formicidae) are a promising source of novel bioactive molecules with potential for clinical and agricultural applications. However, despite the rich diversity of ant species, only a fraction of this vast resource has been thoroughly examined in bioprospecting programs. Previous studies focusing on the venom of Central European ants (subfamily Myrmicinae) identified a number of short linear decapeptides and nonapeptides resembling antimicrobial peptides (AMPs). Here, we describe the in silico approach and bioactivity profiling of 10 novel AMP-like peptides from the fellow Central European myrmicine ants Myrmica rubra and Myrmica ruginodis. Using the sequences of known ant venom peptides as queries, we screened the venom gland transcriptomes of both species. We found transcripts of nine novel decapeptides and one novel nonapeptide. The corresponding peptides were synthesized for bioactivity profiling in a broad panel of assays consisting of tests for cytotoxicity as well as antiviral, insecticidal, and antimicrobial activity. U-MYRTX-Mrug5a showed moderately potent antimicrobial effects against several bacteria, including clinically relevant pathogens such as Listeria monocytogenes and Staphylococcus epidermidis, but high concentrations showed negligible cytotoxicity. U-MYRTX-Mrug5a is, therefore, a probable lead for the development of novel peptide-based antibiotics. Full article
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Review

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20 pages, 421 KiB  
Review
Zootoxins and Domestic Animals: A European View
by Andras-Laszlo Nagy, Sabrina Ardelean, Ronan J. J. Chapuis, Juliette Bouillon, Dalma Pivariu, Beatrice De Felice, Mirko Bertazzo, Paola Fossati, Leon J. Spicer, Alexandra Iulia Dreanca and Francesca Caloni
Toxins 2024, 16(1), 48; https://doi.org/10.3390/toxins16010048 - 16 Jan 2024
Viewed by 1373
Abstract
Zootoxins are produced by venomous and poisonous species and are an important cause of poisoning in companion animals and livestock in Europe. Little information about the incidence of zootoxin poisoning is available in Europe, with only a few case reports and review papers [...] Read more.
Zootoxins are produced by venomous and poisonous species and are an important cause of poisoning in companion animals and livestock in Europe. Little information about the incidence of zootoxin poisoning is available in Europe, with only a few case reports and review papers being published. This review presents the most important zootoxins produced by European venomous and poisonous animal species responsible for poisoning episodes in companion animals and livestock. The main zootoxin-producing animal species, components of the toxins/venoms and their clinical effects are presented. The most common zootoxicoses involve terrestrial zootoxins excreted by the common toad, the fire salamander, the pine processionary caterpillar, and vipers. The lack of a centralized reporting/poison control system in Europe makes the evaluation of the epidemiology of zootoxin-induced poisonings extremely difficult. Even if there are many anecdotal reports in the veterinary community about the exposure of domestic animals to terrestrial and marine zootoxins, the number of published papers regarding these toxicoses is low. Climate change and its consequences regarding species distribution and human-mediated transportation are responsible for the emerging nature of some intoxications in which zootoxins are involved. Although new venomous or poisonous animal species have emerged in regions where they were previously unreported, zootoxins produced by native species remain the main concern in Europe. The diversity of poisonous and venomous animal species and the emerging nature of certain poisonings warrant the continuous update to such knowledge by veterinary professionals and animal owners. This review offers an overview about zootoxin-related poisonings in domestic animals in Europe and also provides important information from a health perspective. Full article
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