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Methods in Enzymology 2006The major virulence factor produced by the bacterium Bacillus thuringiensis (Bt) is a pore-forming toxin called crystal (Cry) toxin, which targets and kills insects and... (Review)
Review
The major virulence factor produced by the bacterium Bacillus thuringiensis (Bt) is a pore-forming toxin called crystal (Cry) toxin, which targets and kills insects and nematodes. To understand how this bacterial toxin interacts with its invertebrate hosts, a genetic screen in C. elegans for nematodes resistant to Bt toxin was carried out. Four of the five genes that mutated to toxin resistance encode glycosyltransferases. These genes were found to participate in the biosynthesis of C. elegans glycosphingolipids. These glycolipids in turn were shown to directly bind Bt toxin. Thus, resistance to Bt toxin in C. elegans can develop as a result of loss of glycolipid receptors for the toxin. Here we describe the isolation of Bt toxin resistance mutants in C. elegans, isolation of C. elegans glycolipids, and their separation by thin-layer chromatography, overlay assays to demonstrate direct binding of Bt toxin to glycolipids, and the purification of specific C. elegans glycolipid species.
Topics: Animals; Bacillus thuringiensis; Bacterial Toxins; Caenorhabditis elegans; Carbohydrates
PubMed: 17132513
DOI: 10.1016/S0076-6879(06)17021-4 -
Advances in Microbial Physiology 2022AB toxins are protein virulence factors secreted by many bacterial pathogens, contributing to the pathogenicity of the cognate bacteria. AB toxins consist of two... (Review)
Review
AB toxins are protein virulence factors secreted by many bacterial pathogens, contributing to the pathogenicity of the cognate bacteria. AB toxins consist of two functionally distinct components: the enzymatic "A" component for pathogenicity and the receptor-binding "B" component for toxin delivery. Consistently, unlike other virulence factors such as effectors, AB toxins do not require additional systems to deliver them to the target host cells. Target host cells are located in the infection site and/or located distantly from infected host cells. The first part of this review discusses the structural and functional features of single-peptide and multiprotein AB toxins in the context of host-microbe interactions, using several well-characterized examples. The second part of this review discusses toxin neutralization strategies, as well as applications of AB toxins relevant to developing intervention strategies against diseases.
Topics: Bacteria; Bacterial Toxins; Host Microbial Interactions; Virulence; Virulence Factors
PubMed: 36167443
DOI: 10.1016/bs.ampbs.2022.06.002 -
Angewandte Chemie (International Ed. in... May 2023Nanodiscs are a compelling nanomedicine platform due to their ultrasmall size and distinct disc shape. Current nanodisc formulations are made primarily with synthetic...
Nanodiscs are a compelling nanomedicine platform due to their ultrasmall size and distinct disc shape. Current nanodisc formulations are made primarily with synthetic lipid bilayers and proteins. Here, we report a cellular nanodisc made with human red blood cell (RBC) membrane (denoted "RBC-ND") and show its effective neutralization against bacterial toxins. In vitro, RBC-ND neutralizes the hemolytic activity and cytotoxicity caused by purified α-toxin or complex whole secreted proteins (wSP) from methicillin-resistant Staphylococcus aureus bacteria. In vivo, RBC-ND confers significant survival benefits for mice intoxicated with α-toxin or wSP in both therapeutic and prevention regimens. Moreover, RBC-ND shows good biocompatibility and biosafety in vivo. Overall, RBC-ND distinguishes itself by inheriting the biological functions of the source cell membrane for bioactivity. The design strategy of RBC-ND can be generalized to other types of cell membranes for broad applications.
Topics: Humans; Animals; Mice; Methicillin-Resistant Staphylococcus aureus; Erythrocytes; Erythrocyte Membrane; Bacterial Toxins; Lipid Bilayers
PubMed: 36853913
DOI: 10.1002/anie.202301566 -
Food and Chemical Toxicology : An... Jun 2024The special issue "New Insight into Mycotoxins and Bacterial Toxins: Toxicity Assessment, Molecular Mechanism and Food Safety" in Food and Chemical Toxicology contains...
New insight into mycotoxins and bacterial toxins: Toxicity assessment, molecular mechanism and food safety (preface to the special issue of food and chemical toxicology on the outcomes of Myco & bacterial toxin).
The special issue "New Insight into Mycotoxins and Bacterial Toxins: Toxicity Assessment, Molecular Mechanism and Food Safety" in Food and Chemical Toxicology contains 19 articles on current hot topics in mycotoxins and bacterial toxins. Dietary exposure to mycotoxins and risk assessments are reported in this issue. Molecular mechanisms of multiple mycotoxins and emerging mechanisms of toxicity are especially concerned by researchers. Moreover, mycotoxin-detoxifying substances and antimicrobial agents are also fully investigated in the context. This special issue will help to further understand the mycotoxins and bacterial toxins, casting new light for the control of food safety.
Topics: Mycotoxins; Bacterial Toxins; Food Safety; Humans; Food Contamination; Animals; Risk Assessment
PubMed: 38614221
DOI: 10.1016/j.fct.2024.114655 -
Frontiers in Cellular and Infection... 2014Toxin-antitoxin (TA) systems are small genetic elements ubiquitous in prokaryotic genomes that encode toxic proteins targeting various vital cellular functions.... (Review)
Review
Toxin-antitoxin (TA) systems are small genetic elements ubiquitous in prokaryotic genomes that encode toxic proteins targeting various vital cellular functions. Typically, toxin activity is controlled by adjacently encoded protein or RNA antitoxins and unleashed as a consequence of genetic fluctuations or stressful conditions. Whereas some TA systems interfere with replication or cell wall synthesis, most of them influence transcriptional and post-transcriptional gene regulation. Antitoxin proteins often act as DNA binding transcriptional regulators and many TA toxins exhibit endoribonuclease activity to selectively degrade different RNA species and thus alter gene expression patterns. Some TA RNases cleave tRNA, tmRNAs or rRNAs, whereas most commonly mRNAs either in association with the ribosome or as free transcripts, are targeted. Examples are provided on how TA toxins differentially shape gene expression in bacterial pathogens by creating specialized ribosomes or by altering the transcriptome and how this may be tied in the control of pathogenicity factors.
Topics: Bacteria; Bacterial Toxins; Gene Expression Regulation; Protein Biosynthesis; RNA Processing, Post-Transcriptional
PubMed: 24524029
DOI: 10.3389/fcimb.2014.00006 -
Methods in Molecular Biology (Clifton,... 2021It is still a challenge to develop needle-free mucosal vaccines. Despite progress in the development of the influenza vaccine, it must be reformulated annually because...
It is still a challenge to develop needle-free mucosal vaccines. Despite progress in the development of the influenza vaccine, it must be reformulated annually because of antigenic changes in circulating influenza viral strains. Due to seasonal drift and shift of circulating strains, the influenza vaccine does not always match the circulating strains, and included adjuvants are not sufficient to induce a protective effect with long-lived memory cells. The adjuvants play a major role in the immune responses to a vaccine. Interestingly, the Bacillus anthracis detoxified anthrax edema toxin, which composes of protective antigen PA and N-fragment of edema factor (EFn), has shown improved effects for humoral and cellular immune responses. Here we describe the design of a universal influenza vaccine construct that consists of three tandem M2e repeats of the influenza antigen plus HA2 and detoxified toxin EFn, which is associated with the PA component, as well as the techniques used to corroborate protection. We present two major parts of description to demonstrate the vaccine strategy, using detoxified anthrax toxin for intranasal delivery of influenza antigen: (1) vaccine candidate design, production, and purification; (2) influenza virus microneutralization assay and cellular responses and lethal challenge with influenza viruses and B. anthracis Sterne spores. In the methods detailed here, we used different versions of the M2e-HA2 proteins.
Topics: Adjuvants, Immunologic; Animals; Antibodies, Bacterial; Antibodies, Neutralizing; Bacterial Toxins; Carrier Proteins; Enzyme-Linked Immunosorbent Assay; Immunization; Influenza Vaccines; Mice; Neutralization Tests; T-Lymphocytes; Vaccination; Vaccines
PubMed: 32959257
DOI: 10.1007/978-1-0716-0795-4_22 -
Journal of Natural Toxins Nov 2000Toxins are non-replicating agents of biological origin. They are non-infectious, non-contagious, and non-curable by antibiotics or chemotherapeutic agents. However,... (Review)
Review
Toxins are non-replicating agents of biological origin. They are non-infectious, non-contagious, and non-curable by antibiotics or chemotherapeutic agents. However, individuals can be protected by vaccination. The multifactorial nature of virulence of toxin and toxin producers, produces comparative and cooperative pathogenesis, and this makes studies all the more difficult. Antibody raised against all components helps in this pursuit. The toxins have been classified into seven different classes and over 44 bacterial toxins have been discussed. The botulinum toxin is by far the most toxic substance in the world. All the toxins produced are either secreted out, called exotoxins (proteins), or are entrapped in the cell membrane, called endotoxins (lipopolysaccharides). These toxins are di-chain molecules, internalized into the cell by receptor mediated endocytosis, and ADP-ribosylation is the most common mode of action. The toxins produced by bacteria are enterotoxins, neurotoxins, cytotoxins, lysins (e.g., hemolysin), gangrene producing toxins. However, a single bacteria often produces more than one toxin. Bacterial toxins, which are primarily harmful, are also being used for the cure of cancer, killing of mosquito larvae, understanding of basic sciences like ADP-ribosylation, etc.
Topics: Animals; Bacterial Toxins; Biological Transport, Active; Cell Cycle; Cell Membrane; Humans; Neoplasms; Permeability; Pest Control; Rabbits
PubMed: 11126516
DOI: No ID Found -
Toxins Jul 2017Several pathogenic bacteria secrete toxins to inhibit the immune system of the infected organism. Frequently, they catalyze a covalent modification of specific proteins.... (Review)
Review
Several pathogenic bacteria secrete toxins to inhibit the immune system of the infected organism. Frequently, they catalyze a covalent modification of specific proteins. Thereby, they block production and/or secretion of antibodies or cytokines. Moreover, they disable migration of macrophages and disturb the barrier function of epithelia. In most cases, these toxins are extremely effective enzymes with high specificity towards their cellular substrates, which are often central signaling molecules. Moreover, they encompass the capacity to enter mammalian cells and to modify their substrates in the cytosol. A few molecules, at least of some toxins, are sufficient to change the cellular morphology and function of a cell or even kill a cell. Since many of those toxins are well studied concerning molecular mechanisms, cellular receptors, uptake routes, and structures, they are now widely used to analyze or to influence specific signaling pathways of mammalian cells. Here, we review the development of immunotoxins and targeted toxins for the treatment of a disease that is still hard to treat: cancer.
Topics: Animals; Antineoplastic Agents; Bacterial Toxins; Humans; Immunotoxins; Neoplasms
PubMed: 28788054
DOI: 10.3390/toxins9080236 -
Nature Communications Nov 2017The Tetraconata (Pancrustacea) concept proposes that insects are more closely related to aquatic crustaceans than to terrestrial centipedes or millipedes. The question...
The Tetraconata (Pancrustacea) concept proposes that insects are more closely related to aquatic crustaceans than to terrestrial centipedes or millipedes. The question therefore arises whether insects have kept crustacean-specific genetic traits that could be targeted by specific toxins. Here we show that a toxin (nigritoxin), originally identified in a bacterial pathogen of shrimp, is lethal for organisms within the Tetraconata and non-toxic to other animals. X-ray crystallography reveals that nigritoxin possesses a new protein fold of the α/β type. The nigritoxin N-terminal domain is essential for cellular translocation and likely encodes specificity for Tetraconata. Once internalized by eukaryotic cells, nigritoxin induces apoptotic cell death through structural features that are localized in the C-terminal domain of the protein. We propose that nigritoxin will be an effective means to identify a Tetraconata evolutionarily conserved pathway and speculate that nigritoxin holds promise as an insecticidal protein.
Topics: Animals; Apoptosis; Arthropods; Bacterial Toxins; Biological Evolution; Crassostrea; Crustacea; Crystallography, X-Ray; Horseshoe Crabs; Larva; Moths; Penaeidae; Protein Folding; Protein Structure, Tertiary; Spodoptera; Vibrio
PubMed: 29093459
DOI: 10.1038/s41467-017-01445-z -
Current Opinion in Cell Biology Aug 2016Bacterial toxins often translocate across a cellular membrane to gain access into the host cytosol, modifying cellular components in order to exert their toxic effects.... (Review)
Review
Bacterial toxins often translocate across a cellular membrane to gain access into the host cytosol, modifying cellular components in order to exert their toxic effects. To accomplish this feat, these toxins traffic to a membrane penetration site where they undergo conformational changes essential to eject the toxin's catalytic subunit into the cytosol. In this brief review, we highlight recent findings that elucidate both the trafficking pathways and membrane translocation mechanisms of toxins that cross the plasma, endosomal, or endoplasmic reticulum (ER) membrane. These findings not only illuminate the specific nature of the host-toxin interactions during entry, but should also provide additional therapeutic strategies to prevent or alleviate the bacterial toxin-induced diseases.
Topics: Animals; Bacterial Toxins; Cell Membrane; Endoplasmic Reticulum; Endosomes; Humans; Intracellular Membranes; Intracellular Space; Protein Transport
PubMed: 27084982
DOI: 10.1016/j.ceb.2016.03.019