Shiga Toxin: A toxin produced by SHIGELLA DYSENTERIAE. It is the prototype of class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA; (RNA, RIBOSOMAL) with PEPTIDE ELONGATION FACTORS.Shiga Toxin 2: A toxin produced by certain pathogenic strains of ESCHERICHIA COLI such as ESCHERICHIA COLI O157. It shares 50-60% homology with SHIGA TOXIN and SHIGA TOXIN 1.Shiga Toxin 1: A toxin produced by certain pathogenic strains of ESCHERICHIA COLI such as ESCHERICHIA COLI O157. It is closely related to SHIGA TOXIN produced by SHIGELLA DYSENTERIAE.Shiga Toxins: A class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA; (RNA, RIBOSOMAL) with PEPTIDE ELONGATION FACTORS. They include SHIGA TOXIN which is produced by SHIGELLA DYSENTERIAE and a variety of shiga-like toxins that are produced by pathologic strains of ESCHERICHIA COLI such as ESCHERICHIA COLI O157.Shiga-Toxigenic Escherichia coli: Strains of ESCHERICHIA COLI with the ability to produce at least one or more of at least two antigenically distinct, usually bacteriophage-mediated cytotoxins: SHIGA TOXIN 1 and SHIGA TOXIN 2. These bacteria can cause severe disease in humans including bloody DIARRHEA and HEMOLYTIC UREMIC SYNDROME.Shigella dysenteriae: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is extremely pathogenic and causes severe dysentery. Infection with this organism often leads to ulceration of the intestinal epithelium.Escherichia coli O157: A verocytotoxin-producing serogroup belonging to the O subfamily of Escherichia coli which has been shown to cause severe food-borne disease. A strain from this serogroup, serotype H7, which produces SHIGA TOXINS, has been linked to human disease outbreaks resulting from contamination of foods by E. coli O157 from bovine origin.Hemolytic-Uremic Syndrome: A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.Escherichia coli Infections: Infections with bacteria of the species ESCHERICHIA COLI.Enterohemorrhagic Escherichia coli: Strains of ESCHERICHIA COLI that are a subgroup of SHIGA-TOXIGENIC ESCHERICHIA COLI. They cause non-bloody and bloody DIARRHEA; HEMOLYTIC UREMIC SYNDROME; and hemorrhagic COLITIS. An important member of this subgroup is ESCHERICHIA COLI O157-H7.Bacterial Toxins: Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases.Cholera Toxin: An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.T-2 Toxin: A potent mycotoxin produced in feedstuffs by several species of the genus FUSARIUM. It elicits a severe inflammatory reaction in animals and has teratogenic effects.Cytotoxins: Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from CYTOSTATIC AGENTS in degree of effect. Some of them are used as CYTOTOXIC ANTIBIOTICS. The mechanism of action of many of these are as ALKYLATING AGENTS or MITOSIS MODULATORS.Trihexosylceramides: Glycosphingolipids which contain as their polar head group a trisaccharide (galactose-galactose-glucose) moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in ceramide trihexosidase, is the cause of angiokeratoma corporis diffusum (FABRY DISEASE).Globosides: Glycosphingolipids containing N-acetylglucosamine (paragloboside) or N-acetylgalactosamine (globoside). Globoside is the P antigen on erythrocytes and paragloboside is an intermediate in the biosynthesis of erythrocyte blood group ABH and P 1 glycosphingolipid antigens. The accumulation of globoside in tissue, due to a defect in hexosaminidases A and B, is the cause of Sandhoff disease.Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally.Prophages: Genomes of temperate BACTERIOPHAGES integrated into the DNA of their bacterial host cell. The prophages can be duplicated for many cell generations until some stimulus induces its activation and virulence.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Vero Cells: A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.Ribosome Inactivating Proteins: N-Glycosidases that remove adenines from RIBOSOMAL RNA, depurinating the conserved alpha-sarcin loop of 28S RIBOSOMAL RNA. They often consist of a toxic A subunit and a binding lectin B subunit. They may be considered as PROTEIN SYNTHESIS INHIBITORS. They are found in many PLANTS and have cytotoxic and antiviral activity.Tetanus Toxin: Protein synthesized by CLOSTRIDIUM TETANI as a single chain of ~150 kDa with 35% sequence identity to BOTULINUM TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal CONVULSIONS.Antitoxins: Antisera from immunized animals that is purified and used as a passive immunizing agent against specific BACTERIAL TOXINS.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Adhesins, Bacterial: Cell-surface components or appendages of bacteria that facilitate adhesion (BACTERIAL ADHESION) to other cells or to inanimate surfaces. Most fimbriae (FIMBRIAE, BACTERIAL) of gram-negative bacteria function as adhesins, but in many cases it is a minor subunit protein at the tip of the fimbriae that is the actual adhesin. In gram-positive bacteria, a protein or polysaccharide surface layer serves as the specific adhesin. What is sometimes called polymeric adhesin (BIOFILMS) is distinct from protein adhesin.Virulence Factors: Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486)Diarrhea: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.Escherichia coli Vaccines: Vaccines or candidate vaccines used to prevent or treat both enterotoxigenic and enteropathogenic Escherichia coli infections.Serotyping: Process of determining and distinguishing species of bacteria or viruses based on antigens they share.Botulinum Toxins, Type A: A serotype of botulinum toxins that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25.Marine Toxins: Toxic or poisonous substances elaborated by marine flora or fauna. They include also specific, characterized poisons or toxins for which there is no more specific heading, like those from poisonous FISHES.Dysentery, Bacillary: DYSENTERY caused by gram-negative rod-shaped enteric bacteria (ENTEROBACTERIACEAE), most often by the genus SHIGELLA. Shigella dysentery, Shigellosis, is classified into subgroups according to syndrome severity and the infectious species. Group A: SHIGELLA DYSENTERIAE (severest); Group B: SHIGELLA FLEXNERI; Group C: SHIGELLA BOYDII; and Group D: SHIGELLA SONNEI (mildest).Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.Shigella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that ferments sugar without gas production. Its organisms are intestinal pathogens of man and other primates and cause bacillary dysentery (DYSENTERY, BACILLARY).Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Bacteriophages: Viruses whose hosts are bacterial cells.Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester.Toxoids: Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. Anatoxin toxoids are distinct from anatoxins that are TROPANES found in CYANOBACTERIA.Hemolysin Proteins: Proteins from BACTERIA and FUNGI that are soluble enough to be secreted to target ERYTHROCYTES and insert into the membrane to form beta-barrel pores. Biosynthesis may be regulated by HEMOLYSIN FACTORS.Edema Disease of Swine: An acute disease of young pigs that is usually associated with weaning. It is characterized clinically by paresis and subcutaneous edema.Coliphages: Viruses whose host is Escherichia coli.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Cattle Diseases: Diseases of domestic cattle of the genus Bos. It includes diseases of cows, yaks, and zebus.Food Microbiology: The presence of bacteria, viruses, and fungi in food and food products. This term is not restricted to pathogenic organisms: the presence of various non-pathogenic bacteria and fungi in cheeses and wines, for example, is included in this concept.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Glycolipids: Any compound containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety such as an acylglycerol (see GLYCERIDES), a sphingoid, a ceramide (CERAMIDES) (N-acylsphingoid) or a prenyl phosphate. (From IUPAC's webpage)HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Clathrin Heavy Chains: The heavy chain subunits of clathrin.RNA, Ribosomal, 28S: Constituent of the 60S subunit of eukaryotic ribosomes. 28S rRNA is involved in the initiation of polypeptide synthesis in eukaryotes.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Adenylate Cyclase Toxin: One of the virulence factors produced by virulent BORDETELLA organisms. It is a bifunctional protein with both ADENYLYL CYCLASES and hemolysin components.Foodborne Diseases: Acute illnesses, usually affecting the GASTROINTESTINAL TRACT, brought on by consuming contaminated food or beverages. Most of these diseases are infectious, caused by a variety of bacteria, viruses, or parasites that can be foodborne. Sometimes the diseases are caused by harmful toxins from the microbes or other chemicals present in the food. Especially in the latter case, the condition is often called food poisoning.P Blood-Group System: A blood group related to the ABO, Lewis and I systems. At least five different erythrocyte antigens are possible, some very rare, others almost universal. Multiple alleles are involved in this blood group.trans-Golgi Network: A network of membrane compartments, located at the cytoplasmic side of the GOLGI APPARATUS, where proteins and lipids are sorted for transport to various locations in the cell or cell membrane.Enteropathogenic Escherichia coli: Strains of ESCHERICHIA COLI characterized by attaching-and-effacing histopathology. These strains of bacteria intimately adhere to the epithelial cell membrane and show effacement of microvilli. In developed countries they are associated with INFANTILE DIARRHEA and infantile GASTROENTERITIS and, in contrast to ETEC strains, do not produce ENDOTOXINS.Trisaccharides: Oligosaccharides containing three monosaccharide units linked by glycosidic bonds.Genes, Bacterial: The functional hereditary units of BACTERIA.Lethal Dose 50: The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.Glycosphingolipids: Lipids containing at least one monosaccharide residue and either a sphingoid or a ceramide (CERAMIDES). They are subdivided into NEUTRAL GLYCOSPHINGOLIPIDS comprising monoglycosyl- and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides; and ACIDIC GLYCOSPHINGOLIPIDS which comprises sialosylglycosylsphingolipids (GANGLIOSIDES); SULFOGLYCOSPHINGOLIPIDS (formerly known as sulfatides), glycuronoglycosphingolipids, and phospho- and phosphonoglycosphingolipids. (From IUPAC's webpage)Endosomes: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Lysogeny: The phenomenon by which a temperate phage incorporates itself into the DNA of a bacterial host, establishing a kind of symbiotic relation between PROPHAGE and bacterium which results in the perpetuation of the prophage in all the descendants of the bacterium. Upon induction (VIRUS ACTIVATION) by various agents, such as ultraviolet radiation, the phage is released, which then becomes virulent and lyses the bacterium.Disease Outbreaks: Sudden increase in the incidence of a disease. The concept includes EPIDEMICS and PANDEMICS.Transcytosis: The transport of materials through a cell. It includes the uptake of materials by the cell (ENDOCYTOSIS), the movement of those materials through the cell, and the subsequent secretion of those materials (EXOCYTOSIS).Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Electrophoresis, Gel, Pulsed-Field: Gel electrophoresis in which the direction of the electric field is changed periodically. This technique is similar to other electrophoretic methods normally used to separate double-stranded DNA molecules ranging in size up to tens of thousands of base-pairs. However, by alternating the electric field direction one is able to separate DNA molecules up to several million base-pairs in length.Protein Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Brefeldin A: A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Siphoviridae: A family of BACTERIOPHAGES and ARCHAEAL VIRUSES which are characterized by long, non-contractile tails.Immunochromatography: A type of affinity chromatography where ANTIBODIES are used in the affinity capture reaction on the solid support, in the mobile phase, or both.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Serum Amyloid P-Component: Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game.O Antigens: The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Butyrates: Derivatives of BUTYRIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxypropane structure.Scorpion Venoms: Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic.GermanyClostridium difficile: A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis (ENTEROCOLITIS, PSEUDOMEMBRANOUS) in patients receiving antibiotic therapy.Pinocytosis: The engulfing of liquids by cells by a process of invagination and closure of the cell membrane to form fluid-filled vacuoles.Antigens, Tumor-Associated, Carbohydrate: Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.Tosylphenylalanyl Chloromethyl Ketone: An inhibitor of Serine Endopeptidases. Acts as alkylating agent and is known to interfere with the translation process.Mycotoxins: Toxic compounds produced by FUNGI.Bacterial Adhesion: Physicochemical property of fimbriated (FIMBRIAE, BACTERIAL) and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Neutral Glycosphingolipids: A subclass of GLYCOSPHINGOLIPIDS containing one or more sugars within their head group connected directly to a ceramide moiety. They consist of monoglycosyl-, and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides.Bacterial Proteins: Proteins found in any species of bacterium.Clathrin: The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.

Vascular ultrastructure and DNA fragmentation in swine infected with Shiga toxin-producing Escherichia coli. (1/321)

Shiga toxins (Stx) produced by Escherichia coli cause systemic vascular damage that manifests as edema disease in swine and hemolytic uremic syndrome in humans. In vitro, Stx inhibit protein synthesis and, depending on circumstances, induce necrosis, apoptosis, or both. The mechanism of in vivo Stx-mediated vascular damage is not known. The ability of Stx to cause apoptosis of vasculature in vivo was studied in pigs with edema disease that was produced by oral inoculation with Stx-producing E. coli. Arterioles of ileum and brain were evaluated by terminal dUTP nick-end labeling (TUNEL) assay for DNA fragmentation in myocytes (10 infected pigs, 5 control pigs) and by transmission electron microscopy for ultrastructural changes characteristic of apoptosis (17 infected pigs, 8 control pigs). In comparison with controls, increased numbers of TUNEL-positive arterioles were detected in 6/10 (60%) subclinically affected pigs 14-15 days after inoculation. Ultrastructurally, lesions in myocytes consisted of lysis (necrosis), with cytoplasmic debris and nuclear fragments contained between intact basement membranes. Endothelial cell changes ranged from acute swelling to necrosis and detachment from basement membrane. Subclinically affected pigs (n = 14) tended to have changes predominantly in myocytes, whereas pigs with clinical illness (n = 3) more commonly had changes in endothelial cells. The arteriolar lesions and clinical signs of edema disease are attributed to the effects of Stx on vasculature. Therefore, our findings suggest that the Stx-induced arteriolar lesions seen in this study were primarily necrotic, not apoptotic. We suspect that necrosis was the principal cause of the DNA fragmentation detected.  (+info)

Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response. (2/321)

Toxin synthesis by Shiga toxin-producing Escherichia coli (STEC) appears to be coregulated through induction of the integrated bacteriophage that encodes the toxin gene. Phage production is linked to induction of the bacterial SOS response, a ubiquitous response to DNA damage. SOS-inducing antimicrobial agents, particularly the quinolones, trimethoprim, and furazolidone, were shown to induce toxin gene expression in studies of their effects on a reporter STEC strain carrying a chromosome-based stx2::lacZ transcriptional fusion. At antimicrobial levels above those required to inhibit bacterial replication, these agents are potent inducers (up to 140-fold) of the transcription of type 2 Shiga toxin genes (stx2); therefore, they should be avoided in treating patients with potential or confirmed STEC infections. Other agents (20 studied) and incubation conditions produced significant but less striking effects on stx2 transcription; positive and negative influences were observed. SOS-mediated induction of toxin synthesis also provides a mechanism that could exacerbate STEC infections and increase dissemination of stx genes. These features and the use of SOS-inducing antibiotics in clinical practice and animal husbandry may account for the recent emergence of STEC disease.  (+info)

Prevalence of non-O157:H7 shiga toxin-producing Escherichia coli in diarrheal stool samples from Nebraska. (3/321)

We determined the prevalence of Shiga toxin-producing Escherichia coli (STEC) in diarrheal stool samples from Nebraska by three methods: cefixime-tellurite sorbitol MacConkey (CT- SMAC) culture, enterohemorrhagic E. coli (EHEC) enzyme immunoassay, and stx1,2 polymerase chain reaction (PCR). Fourteen (4.2%) of 335 specimens were positive by at least one method (CT-SMAC culture [6 of 14], EHEC enzyme immunoassay [13 of 14], stx1,2 PCR [14 of 14]). Six contained serogroup O157, while non-O157 were as prevalent as O157 serogroups.  (+info)

Detection and characterization of Shiga toxin-producing Escherichia coli from seagulls. (4/321)

Shiga toxin (Stx)-producing Escherichia coli (STEC) strains isolated from a seagull in Japan were examined. A total of 50 faecal samples was collected on a harbour bank in Hokkaido, Japan, in July 1998. Two different STEC strains, whose serotypes were O136:H16 and O153:H-, were isolated from the same individual by PCR screening; both of them were confirmed by ELISA and Vero cell cytotoxicity assay to be producing active Stx2 and Stx1, respectively. They harboured large plasmids, but did not carry the haemolysin or eaeA genes of STEC O157:H7. Based on their plasmid profiles, antibiotic resistance patterns, pulsed-field gel electrophoresis analysis (PFGE), and the stx genes sequences, the isolates were different. Phylogenic analysis of the deduced Stx amino acid sequences demonstrated that the Stx toxins of seagull-origin STEC were closely associated with those of the human-origin, but not those of other animal-origin STEC. In addition, Stx2phi-K7 phage purified from O136 STEC resembled Stx2phi-II from human-origin O157:H7, and was able to convert non-toxigenic E. coli to STEC. These results suggest that birds may be one of the important carriers in terms of the distribution of STEC.  (+info)

Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. (5/321)

A large number of plant and bacterial toxins with enzymatic activity on intracellular targets are now known. These toxins enter cells by first binding to cell surface receptors, then they are endocytosed and finally they become translocated into the cytosol from an intracellular compartment. In the case of the plant toxin ricin and the bacterial toxin Shiga toxin, this happens after retrograde transport through the Golgi apparatus and to the endoplasmic reticulum. The toxins are powerful tools to reveal new pathways in intracellular transport. Furthermore, knowledge about their action on cells can be used to combat infectious diseases where such toxins are involved, and a whole new field of research takes advantage of their ability to enter the cytosol for therapeutic purposes in connection with a variety of diseases. This review deals with the mechanisms of entry of ricin and Shiga toxin, and the attempts to use such toxins in medicine are discussed.  (+info)

Shiga toxin activates p38 MAP kinase through cellular Ca(2+) increase in Vero cells. (6/321)

We examined whether the mitogen-activated protein kinase (MAPK) pathway is involved in Shiga toxin (Stx)-induced Vero cell injury. Consonant with cell injury, Stx caused a transient extracellular signal-regulated kinase1/2 (ERK1/2) and a sustained p38 MAPK phosphorylation. p38 MAPK inhibitors (SB 203580 and PD 169316), but not an ERK1/2 kinase inhibitor (PD 98059), partially inhibited the Stx-induced cell death. BAPTA-AM, a Ca(2+) chelator, reduced both cell injury and p38 MAPK phosphorylation. Antioxidants reduced Stx1-induced p38 MAPK phosphorylation. These data indicate that Stx activates p38 MAPK through an increase in intracellular Ca(2+) and reactive oxygen species, and this signaling is involved in Stx-induced cell death.  (+info)

Rab11 regulates the compartmentalization of early endosomes required for efficient transport from early endosomes to the trans-golgi network. (7/321)

Several GTPases of the Rab family, known to be regulators of membrane traffic between organelles, have been described and localized to various intracellular compartments. Rab11 has previously been reported to be associated with the pericentriolar recycling compartment, post-Golgi vesicles, and the trans-Golgi network (TGN). We compared the effect of overexpression of wild-type and mutant forms of Rab11 on the different intracellular transport steps in the endocytic/degradative and the biosynthetic/exocytic pathways in HeLa cells. We also studied transport from endosomes to the Golgi apparatus using the Shiga toxin B subunit (STxB) and TGN38 as reporter molecules. Overexpression of both Rab11 wild-type (Rab11wt) and mutants altered the localization of the transferrrin receptor (TfR), internalized Tf, the STxB, and TGN38. In cells overexpressing Rab11wt and in a GTPase-deficient Rab11 mutant (Rab11Q70L), these proteins were found in vesicles showing characteristics of sorting endosomes lacking cellubrevin (Cb). In contrast, they were redistributed into an extended tubular network, together with Cb, in cells overexpressing a dominant negative mutant of Rab11 (Rab11S25N). This tubularized compartment was not accessible to Tf internalized at temperatures <20 degrees C, suggesting that it is of recycling endosomal origin. Overexpression of Rab11wt, Rab11Q70L, and Rab11S25N also inhibited STxB and TGN38 transport from endosomes to the TGN. These results suggest that Rab11 influences endosome to TGN trafficking primarily by regulating membrane distribution inside the early endosomal pathway.  (+info)

Molecular and phenotypic characterization of potentially new Shigella dysenteriae serotype. (8/321)

From September 1997 to November 1998, the French National Center for Salmonella and Shigella received 22 Shigella isolates recovered from 22 different patients suffering from dysentery. None of these isolates reacted with any of the antisera used to identify established Shigella serotypes, but all of them agglutinated in the presence of antisera to a previously described potentially new Shigella dysenteriae serotype (represented by strain 96-204) primarily isolated from stool cultures of imported diarrheal cases in Japan. All French isolates, as well as strain 96-204, showed biochemical reactions typical of S. dysenteriae and gave positive results in a PCR assay for detection of the plasmid ipaH gene coding for invasiveness. No Shiga toxin gene was detected by PCR. These isolates were indistinguishable by molecular analysis of ribosomal DNA (ribotyping) and seemed to be related to S. dysenteriae serotypes 3 and 12. However, further characterization by restriction of the amplified O-antigen gene cluster clearly distinguished this new serotype from all other Shigella or Escherichia coli serotypes.  (+info)

  • Furthermore, using a quantitative biochemical assay, it was found that the amount of receptor-binding B-subunit of Shiga toxin reaching the trans-Golgi/TGN membranes was decreased in Rab12-depleted cells, and that cells were partially protected against intoxication by Shiga-like toxin 1 under these conditions. (
  • Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. (
  • Induction of cytokines in a human colon epithelial cell line by Shiga toxin 1 (Stx1) and Stx2 but not by non-toxic mutant Stx1 which lacks N-glycosidase activity," FEBS Letters , vol. 442, no. 2-3, pp. 231-234, 1999. (
  • There are two major antigenic forms of Shiga toxin (Stx), Stx1 and Stx2, which bind the same receptor and act on the same target but nonetheless differ in potency. (
  • Even though the reindeers were not interacting with any other ruminants, which are considered to be a major reservoir of Shiga toxin containing bacteria, the stx1 gene was detected in 9 out of 10 tested samples, and the stx2 subtype c was found in five tested samples. (
  • Accordingly, these treatments displaced both toxin variants from neutrophils and, upon challenge with Stx1 or Stx2, neutrophils displayed the same pattern of cytokine expression as in response to LPS (assessed by quantitative RT-PCR, ELISA, or multiplexed Luminex-based immunoassays). (
  • could also carry different Shiga toxin (stx) genes and their variants (stx1 and/or stx2) (1,2). (
  • In this study, a quantitative real-time PCR (qPCR) method was developed as a molecular method to detect and quantify Shiga toxin genes stx1 and stx2 and the intimin gene eae. (
  • The Shiga-like toxin is associated with hemolytic-uremic syndrome. (
  • Shiga toxins (Stxs) expressed by STEC are highly cytotoxic class II ribosome-inactivating proteins and primary virulence factors responsible for major clinical signs of Stx-mediated pathogenesis, including bloody diarrhea, hemolytic uremic syndrome (HUS), and neurological complic. (
  • The severe complications associated with toxin production and release range from bloody diarrhea and hemorrhagic colitis to hemolytic-uremic syndrome, kidney failure, and neurological issues. (
  • Antibiotics may increase production and release of the Shiga toxin and put patients at higher risk of developing serious complications like hemolytic uremic syndrome (HUS), and they have not been shown to improve illness. (
  • More than 50% of patients with non-Shiga toxin-associated hemolytic uremic syndrome (non-Stx-HUS) progress to ESRD. (
  • Two strains of the Shiga toxin are responsible for approximately 265,000 intestinal infections each year in the U.S. The strains have caused multiple food-borne outbreaks prompted by the consumption of undercooked meat, raw milk, lettuce, spinach and other foods. (
  • The SHIGA TOXIN QUIK CHEK provides results up to 24 hours before other rapid tests, enabling clinicians to initiate patient care sooner and minimize the potential for broader bacterial outbreaks. (
  • By narrowing the diagnostic window from a day to 30 minutes, the SHIGA TOXIN QUIK CHEK promises to be a significant help to clinicians, facilitating more rapid patient care that leads to better outcomes, improving workflows, and reducing the potential for broader outbreaks. (
  • Several other strains, though, have led to severe outbreaks, and SHIGA TOXIN QUIK CHEK detects toxins from both O157 and non-O157 strains. (
  • This study investigated the prevalence of Shiga toxin-producing bacteria in stool samples of patients with diarrhoea associated with outbreaks of foodborne illness in the Islamic Republic of Iran. (
  • A total of 532 stool and rectal swab samples from 70 sporadic outbreaks during May 2014 to August 2015 were examined for infection with Shiga toxin-producing bacteria. (
  • The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. (
  • Stxs are A-B-type toxins which bind to the host glycolipid Gb3 ( 11 ). (
  • However, the Stxs are now classified as select agents, and specific rules govern the distribution of both the toxin and clones of the toxin. (
  • In this study, 105 STEC O157:H7 and O157:H − strains isolated from cultures sent from Finnish hospital laboratories to the Laboratory of Enteric Pathogens, National Public Health Institute ( 9 ), during 1990 to 1999 were phage typed, genotyped by PFGE, and investigated for Shiga toxin variant genes by PCR with restriction fragment length polymorphism. (
  • Though the study was done in mice, the researchers said manganese may be effective at treating Shiga toxin infections in humans, which afflict more than 150 million people each year, many in the developing world. (
  • Humans may not be the major target of this toxin," explains Koudelka. (
  • Humans and some other animals have receptors on the lining of their blood vessels that make them vulnerable to this toxin, while other animals are immune because there are no receptors for the toxin to lock on to. (
  • Shiga toxin causes diseases in humans ranging from mild diarrhoea to HUS, with a mortality rate up to 10 % among young children and the elderly. (
  • An inexpensive, accessible treatment - not a designer drug - is the ideal solution, because Shiga toxin infections plague so many people in developing nations, he said. (
  • The findings could pave the way for future research aimed at creating an inexpensive treatment for infections caused by bacteria that produce the lethal Shiga toxin. (
  • Infections with Shiga toxin (STx)-producing bacteria cause more than a million deaths each year and have no definitive treatment. (
  • Cooperation of Shiga toxins with other virulence factors, such as aggregative adhesin and intimin (eae), could induce more severe disease in infected patients (3). (
  • Tumor necrosis factor alpha increases human cerebral endothelial cell Gb3 and sensitivity to Shiga toxin," Infection and Immunity , vol. 69, no. 3, pp. 1889-1894, 2001. (
  • Shiga toxin 1-induced inflammatory response in lipopolysaccharide-sensitized astrocytes is mediated by endogenous tumor necrosis factor alpha," Infection and Immunity , vol. 78, no. 3, pp. 1193-1201, 2010. (
  • It has been suggested by some researchers that the gene coding for Shiga-like toxin comes from a toxin-converting lambdoid bacteriophage, such as H-19B or 933W, inserted into the bacteria's chromosome via transduction. (
  • Bacteria that carry a virus (a bacteriophage) that packs the Shiga toxin gene (Stx) may depend on it for protection from bacterial predators like the ciliated protozoan Tetrahymena. (
  • We then relate the abundance of Shiga toxin in the environment to work that demonstrates that the genetic mechanisms underlying the production of Shiga toxin genes are modified and embellished beyond the classical microbial gene regulatory paradigms in a manner that apparently "fine tunes" the trigger to modulate the amount of toxin produced. (
  • Shiga toxin (Stx) is the most important virulence factor of STEC and is encoded by stx, which is introduced into STEC genome by bacteriophages through gene transduction. (
  • In this study, in situ hybridization using DNA probe of shiga toxin was used for the isolation of STEC from the PCR-positive stool and -Sequenbe analysis of a part of shiga toxin gene was performed. (
  • A joint effort by the Uniformed Services University of the Health Sciences (USU) and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF) to license assays that allow for the rapid detection of Shiga toxin has received the 2015 Federal Laboratory Consortium Award for Excellence in Technology Transfer. (
  • The first is a detection technology used in food and clinical samples, while the second is a diagnostic assay that uses monoclonal antibodies, developed at USU, to detect Shiga toxins. (
  • Whether these regulatory differences enable the type I and type II groups of Shiga-like toxins to perform different roles in the pathogenesis of infectious diseases remains to be established. (
  • Cholera toxin is released from the periplasm by a type 2 secretion system ( 27 ), while pertussis toxin uses a type 4 secretion system ( 35 ). (
  • This review summarises current knowledge about the influence of the intestinal environment on Stx production and release, Stx interaction with intestinal epithelial cells and intracellular uptake, and toxin translocation into underlying tissues. (
  • However, EPEC O103 were isolated from a variety of sheep products from various industrial establishments and many of these could not be epidemiologically linked to the human cases, indicating an unknown ubiquitous sheep reservoir of EPEC O103 or an unexpected high prevalence of extremely unstable toxin-producing O103 (STEC). (
  • Currently, if an infected person is given an antibiotic, the antibiotic kills the bacteria that produce the toxin. (
  • Treatment for people with this toxin in their bodies relies on providing supportive therapy to help the body recover while also eliminating the bacteria so they cannot continue to produce the toxin. (