• Diphtheria toxin, an exotoxin secreted by Corynebacterium that causes disease in humans by inhibiting protein synthesis, enters the cell via receptor-mediated endocytosis. (rcsb.org)
  • For the first time, we present the high-resolution structure of the diphtheria toxin at a mildly acidic pH (5-6) and compare it to the structure at neutral pH (7). (rcsb.org)
  • The overall results imply that the membrane interactions of the T-domain are critical in ensuring the proper conformational changes required for the preparation of the diphtheria toxin for the cellular entry. (rcsb.org)
  • During intoxication of a cell, the translocation (T) domain of the diphtheria toxin helps the passage of the catalytic domain across the membrane of the endosome into the cytoplasm. (pasteur.fr)
  • Anthrax toxin allows the bacteria to evade the immune system, proliferate, and ultimately kill the host animal. (wikipedia.org)
  • Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and the internal organs. (transcend.org)
  • Engineering Bacterial Toxin to Measure Cholesterol Accessibility on Cell Membranes: Perfringolysin O (PFO) is a Cholesterol-dependent Cytolysin (CDC) secreted by Clostridium perfringens, the pathogenic bacteria that cause gas gangrene. (umass.edu)
  • During oral dysbiosis and periodontitis, local inflammation in periodontal tissue and permeability of local capillaries are enhanced, therefore bacteria from oral microbiome and bacteria-released toxins can enter the systemic circulation. (degruyter.com)
  • Translocation of bacteria from oral cavity to intestine might exacerbate gut dysbiosis. (degruyter.com)
  • When tight junction proteins are affected by mycotoxins more translocation of bacteria and toxins will take place, resulting in an increased immune response and a state of inflammation, also referred to as leaky gut. (allaboutfeed.net)
  • When mycotoxins are present in the lumen and down-regulate the expression of tight junction protein genes, these tight junctions will less be sealed and will allow more bacteria and toxins that are present in the lumen towards the lamina propria to pass through, so called translocation, resulting in decreased resistance. (allaboutfeed.net)
  • When more toxins and bacteria are passing the gut barrier they will trigger pro-inflammatory cytokines and eventually will lead to inflammation, which again will result in more damage to the cell lining and leakage, which is a vicious circle. (allaboutfeed.net)
  • Decreased resistance or increased permeability, not only leads to increased translocation of bacteria, but also to nutrient leakage. (allaboutfeed.net)
  • As time goes on, the microbiome can veer off in a very different direction from 'normal,' which can cause inflammation of the GI tract, and consequent translocation of bacteria or bacterial toxins into the blood. (farnam.com)
  • B) In a diseased state, regardless of the initiating cause, the decreased production of antimicrobial peptides and mucus leads to increased intestinal permeability and translocation of bacteria. (todaysveterinarypractice.com)
  • Gut-barrier disruption leads to translocation of dangerous intraluminal components, such as bacteria and their components, into the gut wall and, most importantly, exposes the immune system to them. (medscape.com)
  • In the gastrointestinal tract, increased permeability possibly allows translocation of the enteric bacteria from the lumen, potentially leading to sepsis or metastatic infection. (msdmanuals.com)
  • We hypothesized that Hsp90, a cytosolic chaperone, is responsible for the translocation of CTA1 across the membrane. (ucf.edu)
  • The B domain includes two functional domains: a receptor-binding domain, which defines the tropism of a toxin for a cell and a translocation domain that delivers the A domain across a lipid bilayer, either on the plasma membrane or the endosome. (springer.com)
  • When food contaminated with BoNTs is ingested the toxin passes through the gastrointestinal tract, transcytosed from gut lumen into general blood circulation, binds to the presynaptic membrane of the neuronal cells and then is internalized by receptor-mediated endocytosis into nerve cells. (nature.com)
  • Earlier Postdoctoral positions involved investigating the translocation of toxins produced by E. coli , through the Gram negative outer membrane with a view to use these molecules as novel antibiotics. (ncl.ac.uk)
  • A biophysics based approach was used to study the mechanism of toxin translocation through the bacterial membrane, spanning techniques including small angle neutron scattering/X-ray scattering, circular dichroism, surface plasmon resonance and isothermal titration calorimetry. (ncl.ac.uk)
  • The subsequent endosomal acidification triggers a series of conformational changes, resulting in the refolding and membrane insertion of the translocation (T-)domain and ultimately leading to the translocation of the catalytic domain into the cytoplasm. (rcsb.org)
  • La photographie montre l'accumulation de p150 Glued à l'avant des cellules en migration, où la protéine pourrait participer à l'ancrage des microtubules à la membrane plasmique. (pasteur.fr)
  • AB-type protein toxins such as cholera toxin (CT) consist of a catalytic A subunit and a cell-binding B subunit. (ucf.edu)
  • Download instantly The Comprehensive Sourcebook of Bacterial Protein Toxins 3rd Edition by Joseph E. Alouf, Michel R. Popoff. (booksca.ca)
  • Botulinum neurotoxins (BoNTs) are protein toxins produced by 50,000 daltons. (cdc.gov)
  • It was originally proposed that CTA1 is thermally stable and that ER chaperones actively unfolded CTA1 for translocation to the cytosol. (ucf.edu)
  • In contrast, we hypothesized that the dissociated CTA1 subunit would unfold spontaneously at 37°C. This study focused on the three conditions linked to CTA1 instability and translocation: (i) CTA1 dissociation from the holotoxin, (ii) the translocation-competent conformation of CTA1, and the extraction of CTA1 from the ER into the cytosol. (ucf.edu)
  • This stabilization resulted in a decrease in translocation from the ER to the cytosol and a block of intoxication, which makes it a viable candidate for a therapeutic. (ucf.edu)
  • Using drug treatments and RNAi, we found that Hsp90 is required for the translocation of CTA1 from the ER lumen to the cytosol, a brand new function for this chaperone. (ucf.edu)
  • The spontaneous unfolding of CTA1 is the key to its v recognition by ERAD and ultimately its translocation into the cytosol. (ucf.edu)
  • Once in the cytosol, the enzymatic components of the toxin disrupts various immune cell functions, namely cellular signaling and cell migration. (wikipedia.org)
  • Yamasaki S, Sato T, Hidaka Y, Ozaki H, Ito H, Hirayama T, Takeda Y, Sugimura T, Tai A, Shimonishi Y (1990) Structure-activity relationship of Escherichia coli heat-stable enterotoxin: Role of Ala residue at position 14 in toxin-receptor interaction. (springer.com)
  • Single cell-based digital PCR detection and association of Shiga toxin-producing Escherichia coli serogroups and major virulence genes. (cdc.gov)
  • In contrast, infant botulism is caused by colonization of the gut by C botulinum, and subsequent production and absorption leads to absorption of the toxin. (medscape.com)
  • Wound botulism may occur if the organism infects a wound and produces the toxin. (medscape.com)
  • [18] The toxin causes the disease botulism . (wikipedia.org)
  • Intoxication with delivering the catalytic light chain (LC) to its target via its N- one of the seven distinct serotypes of BoNT (A-G) causes botulism, terminal translocation domain (HN) [6]. (cdc.gov)
  • Increased intestinal permeability increases translocation of toxins such as lipopolysaccharides that are produced by gut microorganism into the body, causing inflammatory injuries in the gut wall. (usda.gov)
  • Inflammatory injury is a characteristic of most gut infections, implying that the increased susceptibility to gut infections of pigs after weaning is mainly due to increased intestinal permeability to toxins and hence inflammatory injury. (usda.gov)
  • Together, these results suggest that berberine can improve the gut health of weaned pigs by reducing permeability of the gut to toxins through reduction of oxidative stress. (usda.gov)
  • This review summarizes the major families of bacterial toxins and also describes the specific structure-function properties of the botulinum neurotoxins. (springer.com)
  • Botulinum neurotoxins (BoNTs) are among the most potent toxins known. (psi.ch)
  • Botulinum neurotoxins (BoNTs) are extremely potent toxins that are capable of causing death or respiratory failure leading to long-term intensive care. (cdc.gov)
  • Arakawa T., Yu J., Langridge W.H. Food plant-delivered cholera toxin B subunit for vaccination and immunotolerization. (laaz.org)
  • Recognition of human and rabbit goal cell glycoconjugates as compared with cholera toxin. (laaz.org)
  • Sun J.B., Czerkinsky C., Holmgren J. Mucosally induced immunological tolerance, regulatory T cells and the adjuvant effect by cholera toxin B subunit. (laaz.org)
  • Isomura I., Yasuda Y., Tsujimura K., Takahashi T., Tochikubo K., Morita A. Recombinant cholera toxin B subunit prompts dendritic cells and enhances antitumor immunity. (laaz.org)
  • George-Chandy A., Eriksson K., Lebens M., Nordstrom I., Schon E., Holmgren J. Cholera toxin B subunit as a carrier molecule promotes antigen presentation and will increase CD40 and CD86 expression on antigen-presenting cells. (laaz.org)
  • It is known that progenitor toxin complex protects the neurotoxin during exposure to harsh conditions found in the stomach and small intestines where it is exposed to acidic pH (2.0) and peptidases like pepsin. (nature.com)
  • Botulinum toxin , or botulinum neurotoxin (commonly called botox ), is a highly potent neurotoxic protein produced by the bacterium Clostridium botulinum and related species. (wikipedia.org)
  • The muscle paralyzing feature of botulinum toxin, when used beneficially, has proven to be useful in more than 50 pathological conditions, including cosmetic applications. (medscape.com)
  • In 1946, Schantz helped isolate botulinum toxin type A in crystalline form. (medscape.com)
  • In the early 1970s, Scott experimented with botulinum toxin type A in monkeys for the treatment of strabismus. (medscape.com)
  • In the mid-1980s, he treated an individual with botulinum toxin for cosmetic reasons. (medscape.com)
  • Carruthers, Carruthers, Brin, and the Columbia University group noticed cosmetic improvement following botulinum toxin injection for facial dystonias and began pursuing this line of investigation in the late 1980s and early 1990s. (medscape.com)
  • The seven main types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and G). [20] [22] New types are occasionally found. (wikipedia.org)
  • Botulinum toxin is used to treat a number of therapeutic indications, many of which are not part of the approved drug label. (wikipedia.org)
  • [46] Botulinum toxin appears to be effective for refractory overactive bladder . (wikipedia.org)
  • [52] [53] AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. (wikipedia.org)
  • Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, Bacillus anthracis-the causative agent of anthrax. (wikipedia.org)
  • Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). (wikipedia.org)
  • Research on anthrax toxin also provides insight into the generation of macromolecular assemblies, and on protein translocation, pore formation, endocytosis, and other biochemical processes. (wikipedia.org)
  • The lethality of the disease is caused by the bacterium's two principal virulence factors: (i) the polyglutamic acid capsule, which is anti-phagocytic, and (ii) the tripartite protein toxin, called anthrax toxin. (wikipedia.org)
  • Anthrax toxin is a mixture of three protein components: (i) protective antigen (PA), (ii) edema factor (EF), and (iii) lethal factor (LF). (wikipedia.org)
  • Anthrax toxin is an A-B toxin. (wikipedia.org)
  • Each individual anthrax toxin protein is nontoxic. (wikipedia.org)
  • Anthrax toxin is of the form A2B, where the two enzymes, EF and LF, are the A components and PA is the B component. (wikipedia.org)
  • citation needed] Anthrax toxin protein components must assemble into holotoxin complexes to function. (wikipedia.org)
  • This process starts when the 83-kDa form of PA, called PA83, binds to an anthrax toxin receptor. (wikipedia.org)
  • Bacterial toxins are often characterized based upon the secretion mechanism that delivers the toxin out of the bacterium, termed types I-VII. (springer.com)
  • BoNT/A, /C, and /E cleave toxin, or contact of the bacterium with a wound [1]. (cdc.gov)
  • Several techniques including disk diffusion and broth microdilution were used to identify patterns of antibiotic resistance, microtiter plate assay to measure biofilm formation, and PCR to evaluate the prevalence of different genes such as virulence factors, toxin-antitoxin systems, resistance to β-lactams and fluoroquinolone antibiotics of E. coli strains. (biomedcentral.com)
  • The evolutionary dynamics of sex chromosomes suggest a mechanism for 'inheritance' turnover of sex-determining genes that is mediated by translocation of a sex-determining enhancer. (nature.com)
  • In some embodiments, one or more genes of interest in the translocation-bearing altered insect population encodes for a disease prevention protein/disease refractory protein, or a gene conferring conditional lethality, inability to undergo diapause, sterility, inability to fly. (justia.com)
  • The toxin-antitoxin system genes ( maz F, ccd AB, and rel B) showed a comparable frequency. (biomedcentral.com)
  • Protein translocation across membranes. (lu.se)
  • Bacterial toxins can be single proteins or oligomeric protein complexes that are organized with distinct AB structure-function properties. (springer.com)
  • Enterocytes contain different surface proteins, such as efflux proteins that are responsible for pumping toxins back to the lumen or tight junction proteins that are responsible for gluing enterocytes together. (allaboutfeed.net)
  • The idea that they play an important role is also based on data that suggest drastically-enhanced oral toxicity of the progenitor toxin compared to the purified BoNT 10 . (nature.com)
  • Vermeulen A.J., Tang Y., Heuck A.P. (2016) Translocation of Toxins by Gram Negative Pathogens Using the Type III Secretion System. (umass.edu)
  • Botulinum toxins are among the most potent toxins known to science. (wikipedia.org)
  • Alcohol consumption alters gut flora, leading to leaky gut syndrome, leading to bacterial translocation, leading to inflammatory changes in the liver and elsewhere. (transcend.org)
  • The actual interface is at the gut barrier, where there needs to be an ideal homeostasis and selectivity mechanism to allow the absorption of healthy nutrients, but on the other hand prevent the penetration of harmful microbes, food antigens, and other proinflammatory factors and toxins. (medscape.com)
  • Towards this aim, we are investigating toxin translocation and toxin/host receptor interactions. (psi.ch)
  • Host factors play very important roles in intoxication by AB toxins and are targets for blocking intoxication. (ucf.edu)
  • [29] Intoxication can occur naturally as a result of either wound or intestinal infection or by ingesting formed toxin in food. (wikipedia.org)
  • Among the many problems this causes, it exposes the liver to toxins and increases the chance of liver injury. (transcend.org)
  • Infection of middle-aged mice with C. difficile led to greater disease compared to young controls, which was associated with increases in C. difficile burden and toxin titers, and elevated bacterial translocation. (listlabs.com)
  • assessed the feasibility of translocation by way of the PA pore for a lot of completely different cargo molecules, from brief or cyclic peptides to small molecule medicine. (laaz.org)
  • In this Review, we describe the intestinal damage that occurs in HIV infection, the evidence for translocation of microbial products into the systemic circulation and the pathways by which these products activate the immune system. (nih.gov)
  • We also discuss novel therapies that disrupt the translocation of microbial products and the downstream effects of microbial translocation. (nih.gov)
  • Disruption of any of these events will confer resistance to the toxin. (ucf.edu)
  • In the endosome, the enzymatic components of the toxin translocate into the cytoplasm of a target cell. (wikipedia.org)
  • The chromosomal translocation generates a translocation-bearing altered insect population, the translocation-bearing altered insect population comprises translocation-bearing individuals that are translocation heterozygotes and translocation-bearing individuals that are translocation homozygotes for the chromosomal translocation, and the translocation-bearing individuals display a fitness that is greater than that of the wildtype (non-translocation-bearing) individuals when challenged in a condition in which a translocation-based drive occurs. (justia.com)
  • In some embodiments, the condition in which translocation-based drive occurs comprises one or more of a population cage, a field cage, or an open environment. (justia.com)
  • Moreover, translocation of oral microbes to the intestine aggravates gut microbiome dysbiosis. (degruyter.com)
  • Accordingly, we used NH4Cl to examine the function of acidic endosomes in Pet translocation (Fig. three). (laaz.org)
  • Structure of the Streptococcus pyogenes NADase translocation domain and its essential role in toxin binding to oropharyngeal keratinocytes. (amedeo.com)
  • CTA1 must maintain an unfolded conformation to keep its translocation-competent state. (ucf.edu)
  • Surprisingly, the TH1 helix maintains its conformation in the crystal of the full-length toxin even at pH 5. (rcsb.org)
  • The free energy profile I am interested in is the translocation of a toxin across a carbon nanotube. (uiuc.edu)
  • Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. (cdc.gov)
  • He also hypothesized possible therapeutic uses of the sausage toxin. (medscape.com)
  • In some embodiments, the fitness is defined as a population genetic behavior, over multiple generations, of translocation chromosomes in populations comprising both translocation-bearing individuals and non-translocation-bearing individuals. (justia.com)
  • Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. (cdc.gov)
  • Muscles weakened by toxin injection recover from paralysis after several months, so injection might seem to need to be repeated, but muscles adapt to the lengths at which they are chronically held, [48] so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect. (wikipedia.org)