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Toxins Apr 2021Abrin, the toxic lectin from the rosary pea plant has gained considerable interest in the recent past due to its potential malevolent use. However, reliable and...
Abrin, the toxic lectin from the rosary pea plant has gained considerable interest in the recent past due to its potential malevolent use. However, reliable and easy-to-use assays for the detection and discrimination of abrin from related plant proteins such as agglutinin or the homologous toxin ricin from are sparse. To address this gap, a panel of highly specific monoclonal antibodies was generated against abrin and the related agglutinin. These antibodies were used to establish two sandwich ELISAs to preferentially detect abrin or agglutinin (limit of detection 22 pg/mL for abrin; 35 pg/mL for agglutinin). Furthermore, an abrin-specific lateral flow assay was developed for rapid on-site detection (limit of detection ~1 ng/mL abrin). Assays were validated for complex food, environmental and clinical matrices illustrating broad applicability in different threat scenarios. Additionally, the antibodies turned out to be suitable for immuno-enrichment strategies in combination with mass spectrometry-based approaches for unambiguous identification. Finally, we were able to demonstrate for the first time how the developed assays can be applied to detect, identify and quantify abrin from a clinical sample derived from an attempted suicide case involving .
Topics: Abrin; Abrus; Antibodies, Monoclonal; Antibody Specificity; Enzyme-Linked Immunosorbent Assay; Feces; Humans; Limit of Detection; Plant Lectins; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Suicide, Attempted; Tandem Mass Spectrometry
PubMed: 33919561
DOI: 10.3390/toxins13040284 -
Toxins Oct 2017Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), and is a potential bioterror weapon. The temperature and pH stability of...
Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), and is a potential bioterror weapon. The temperature and pH stability of abrin was evaluated with an in vitro cell free translation (CFT) assay, a Vero cell culture cytotoxicity assay, and an in vivo mouse bioassay. pH treatment of abrin had no detrimental effect on its stability and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing temperatures did not completely abrogate protein translation. In both the cell culture cytotoxicity model and the mouse bioassay, abrin's toxic effects were completely abrogated if the toxin was exposed to temperatures of 74 °C or higher. In the cell culture model, 63 °C-treated abrin had a 30% reduction in cytotoxicity which was validated in the in vivo mouse bioassay with all mice dying but with a slight time-to-death delay as compared to the non-treated abrin control. Since temperature inactivation did not affect abrin's ability to inhibit protein synthesis (A-chain), we hypothesize that high temperature treatment affected abrin's ability to bind to cellular receptors (affecting B-chain). Our results confirm the absolute need to validate in vitro cytotoxicity assays with in vivo mouse bioassays.
Topics: Abrin; Animals; Biological Availability; Cell Survival; Chlorocebus aethiops; Female; Hydrogen-Ion Concentration; Lethal Dose 50; Mice; Temperature; Toxins, Biological; Vero Cells
PubMed: 29027937
DOI: 10.3390/toxins9100320 -
Frontiers in Immunology 2022Abrin, a type-II ribosome inactivating protein from the seed of , is classified as a Category B bioterrorism warfare agent. Due to its high toxicity, ingestion by...
Abrin, a type-II ribosome inactivating protein from the seed of , is classified as a Category B bioterrorism warfare agent. Due to its high toxicity, ingestion by animals or humans will lead to death from multiple organ failure. Currently, no effective agents have been reported to treat abrin poisoning. In this study, a novel anti-abrin neutralizing antibody (S008) was humanized using computer-aided design, which possessed lower immunogenicity. Similar to the parent antibody, a mouse anti-abrin monoclonal antibody, S008 possessed high affinity and showed a protective effect against abrin both and , and protected mice that S008 was administered 6 hours after abrin. S008 was found that it did not inhibit entry of abrin into cells, suggesting an intracellular blockade capacity against the toxin. In conclusion, this work demonstrates that S008 is a high affinity anti-abrin antibody with both a neutralizing and protective effect and may be an excellent candidate for clinical treatment of abrin poisoning.
Topics: Abrin; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antitoxins; Female; Mice; Mice, Inbred BALB C; Poisoning; Survival Rate
PubMed: 35185923
DOI: 10.3389/fimmu.2022.831536 -
Molecules (Basel, Switzerland) Nov 2016This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth... (Review)
Review
This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery. Studies on RIP/cell interactions were able to detail the endocytosis and intracellular routing of ricin, thus increasing our knowledge of how cells handle exogenous proteins. The identification of new RIPs and the finding that most RIPs are single-chain polypeptides, together with their genetic sequencing, has aided in the development of new phylogenetic theories. Overall, the biological properties of these proteins, including their abortifacient, anticancer, antiviral and neurotoxic activities, suggest that RIPs could be utilized in agriculture and in many biomedical fields, including clinical drug development.
Topics: Animals; Endocytosis; Humans; Immunotoxins; Phylogeny; Plant Proteins; Protein Conformation; Ribosome Inactivating Proteins
PubMed: 27898041
DOI: 10.3390/molecules21121627 -
Toxins Nov 2019The sequenced genome and the leaf transcriptome of a near relative of and was analyzed to characterize the genetic basis of toxin gene expression. From the...
The sequenced genome and the leaf transcriptome of a near relative of and was analyzed to characterize the genetic basis of toxin gene expression. From the high-quality genome assembly, a total of 26 potential coding regions were identified that contain genes with abrin-like, pulchellin-like, and agglutinin-like homology, with full-length transcripts detected in leaf tissue for 9 of the 26 coding regions. All of the toxin-like genes were identified within only five isolated regions of the genome, with each region containing 1 to 16 gene variants within each genomic region (<1 Mbp). The cultivar sequenced here contains genes which encode for proteins that are homologous to certain abrin and prepropulchellin genes previously identified, and we observed substantial diversity of genes and predicted gene products in and previously characterized toxins. This suggests diverse toxin repertoires within , potentially the results of rapid toxin evolution.
Topics: Abrin; Abrus; DNA, Plant; Genome, Plant; Phylogeny; Plant Leaves; Plant Lectins; Toxins, Biological; Transcriptome; Whole Genome Sequencing
PubMed: 31775284
DOI: 10.3390/toxins11120691 -
Antibodies (Basel, Switzerland) Apr 2020Abrin, a toxin isolated from the seeds of (jequirity pea) is considered a biological threat agent by the Center for Disease Control and Prevention. To date, there is no...
Abrin, a toxin isolated from the seeds of (jequirity pea) is considered a biological threat agent by the Center for Disease Control and Prevention. To date, there is no effective postexposure treatment for abrin poisoning, and efforts are being made to develop an efficient vaccine and measures for postexposure therapy. Epitope mapping is widely applied as an efficient tool for discovering the antigenic moieties of toxins, thus providing invaluable information needed for the development of vaccines and therapies. Aiming to identify the immunodominant epitopes of abrin, several neutralizing antiabrin polyclonal antibodies were screened using a set of 15-mer peptides spanning the amino acid sequence of either the A or B subunits of abrin. Analysis of the antibody-binding pattern revealed 11 linear epitopes for the A subunit and 14 epitopes for the B subunit that are located on the surface of the toxin and thus accessible for antibody interactions. Moreover, the spatial location of several of these epitopes suggests they may block the galactose-binding pockets or the catalytic domain, thus neutralizing the toxin. These findings provide useful information and suggest a possible strategy for the development and design of an improved abrin-based vaccine and therapeutic antibodies.
PubMed: 32349421
DOI: 10.3390/antib9020011 -
Archiwum Medycyny Sadowej I Kryminologii 2020In the novel "The Name of the Rose" by Umberto Eco, a fanatical monk laced the pages of a book with a poison, which led to the death of several monks in a medieval... (Review)
Review
In the novel "The Name of the Rose" by Umberto Eco, a fanatical monk laced the pages of a book with a poison, which led to the death of several monks in a medieval monastery. Based on modern toxicological knowledge, an attempt can be made to determine whether there exists a substance meeting the criteria of the poison described in the novel. To this end, toxicological literature on the lethal doses of plant-derived poisons and their duration of action was reviewed. Cowbane (Cicuta virosa), a plant used for preparing poisonous potions, contains cicutoxin which kills at a dose of 500 mg. Similar toxicity is displayed by water dropwort (Oenanthe crocata) and Cerbera odollam growing in India and Madagascar. Hemlock (Conium maculatum) contains coniine which is able to kill a victim after exposure to a dose as low as 100 to 200 mg. Morphine found in opium poppy (Papaver somniferum) and colchicine contained in autumn crocus (Colchicum autumnale) produce lethal effects at similar doses. So do more exotic plants such as Calabar bean (Physostigma venenosum) which contains physostygmine. Two other exotic plants that need to be mentioned in this context are far more poisonous. They include Saint Ignatius's bean (Strychnos ignatii) and strychnine tree (Strychnos nux-vomica). Both contain strychnine, the lethal dose of which is 30 mg. Death cap (Amanita phalloides) might also be considered in this context, but despite being lethal at a dose of 20 mg, amanitin contained in this fungus takes a few days to kill a victim, so the effect is considerably slower than that experienced by the monks in Eco's novel. A dose of 10 mg is sufficient to kill a human with any of four other plant-derived poisons: antiarin, atropine, digoxin and strophantin. Aconitum (Aconitum napellus), also known as monkshood, contains aconitine and is an even more deadly plant, with the lethal dose for humans being only 2 mg. Ricin and abrin are ranked even higher in the list of plant-derived toxins, as they are able to kill in doses lower than 1 mg. However, they could not have been used by the murderer in "The Name of the Rose", as they cause death only several days after ingestion. To conclude, the plant that best matches the criteria mentioned in the novel is Aconitum.
PubMed: 34431644
DOI: 10.5114/amsik.2020.104944 -
Sensors (Basel, Switzerland) May 2022Ricin and abrin are phytotoxins that can be easily used as biowarfare and bioterrorism agents. Therefore, developing a rapid detection method for both toxins is of great...
Ricin and abrin are phytotoxins that can be easily used as biowarfare and bioterrorism agents. Therefore, developing a rapid detection method for both toxins is of great significance in the field of biosecurity. In this study, a novel nanoforest silicon microstructure was prepared by the micro-electro-mechanical systems (MEMS) technique; particularly, a novel microfluidic sensor chip with a capillary self-driven function and large surface area was designed. Through binding with the double antibodies sandwich immunoassay, the proposed sensor chip is confirmed to be a candidate for sensing the aforementioned toxins. Compared with conventional immunochromatographic test strips, the proposed sensor demonstrates significantly enhanced sensitivity (≤10 pg/mL for both toxins) and high specificity against the interference derived from juice or milk, while maintaining good linearity in the range of 10-6250 pg/mL. Owing to the silicon nanoforest microstructure and improved homogeneity of the color signal, short detection time (within 15 min) is evidenced for the sensor chip, which would be helpful for the rapid tracking of ricin and abrin for the field of biosecurity.
Topics: Abrin; Microfluidics; Ricin; Silicon; Toxins, Biological
PubMed: 35591151
DOI: 10.3390/s22093461 -
International Journal of Molecular... Mar 2019Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as "Chemicals produced by living organisms that have toxic... (Review)
Review
Biological toxins are a heterogeneous group produced by living organisms. One dictionary defines them as "Chemicals produced by living organisms that have toxic properties for another organism". Toxins are very attractive to terrorists for use in acts of bioterrorism. The first reason is that many biological toxins can be obtained very easily. Simple bacterial culturing systems and extraction equipment dedicated to plant toxins are cheap and easily available, and can even be constructed at home. Many toxins affect the nervous systems of mammals by interfering with the transmission of nerve impulses, which gives them their high potential in bioterrorist attacks. Others are responsible for blockage of main cellular metabolism, causing cellular death. Moreover, most toxins act very quickly and are lethal in low doses (LD < 25 mg/kg), which are very often lower than chemical warfare agents. For these reasons we decided to prepare this review paper which main aim is to present the high potential of biological toxins as factors of bioterrorism describing the general characteristics, mechanisms of action and treatment of most potent biological toxins. In this paper we focused on six most danger toxins: botulinum toxin, staphylococcal enterotoxins, toxins, ricin, abrin and T-2 toxin. We hope that this paper will help in understanding the problem of availability and potential of biological toxins.
Topics: Abrin; Animals; Bacterial Toxins; Bioterrorism; Chemical Warfare Agents; Humans; Lethal Dose 50; Models, Molecular; Ricin; T-2 Toxin
PubMed: 30857127
DOI: 10.3390/ijms20051181 -
Toxins Nov 2017Abrin, a member of the ribosome-inactivating protein family, is produced by the plant. Having the potential to pose a severe threat to both human and animal health,...
Abrin, a member of the ribosome-inactivating protein family, is produced by the plant. Having the potential to pose a severe threat to both human and animal health, abrin is classified as a Select Agent by the U.S. Department of Health and Human Services. However, an immunoassay that is specific for intact abrin holotoxin has not yet been reported. In this study, seven new monoclonal antibodies (mAbs), designated as Abrin-1 through Abrin-7 have been developed. Isotyping analyses indicate these mAbs have IgG1, IgG2a, or IgG2b heavy-chains and kappa light-chains. Western blot analyses identified two abrin A-chain specific mAbs, Abrin-1 and Abrin-2, and four B-chain specific mAbs (Abrin-3, -5, -6, and -7). A sandwich enzyme-linked immunosorbent assay (ELISA), capable of detecting a mixture of abrin isoforms and agglutinins was developed using B-chain specific Abrin-3 for capture and A-chain specific Abrin-2 as detector. The ELISA is highly sensitive and detects 1 ng/mL of the abrin holotoxin in phosphate-buffered saline, nonfat milk, and whole milk, significantly below concentrations that would pose a health concern for consumers. This ELISA also detects native abrin in plant extracts with a very low background signal. The new abrin mAbs and ELISA should be useful for detecting this potent toxin in the milk supply chain and other complex matrices.
Topics: Abrin; Abrus; Animals; Antibodies, Monoclonal; Ricinus communis; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin G; Mice; Mice, Inbred BALB C; Milk; Plant Extracts; Ricin; Seeds
PubMed: 29182545
DOI: 10.3390/toxins9120386