is diphtheria an ab toxin

How does the toxin cause diphtheria?

The toxin causes the disease in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis. Diphtheria toxin is a single polypeptide chain of 535 amino acids consisting of two subunits linked by disulfide bridges, known as an A-B toxin.

What is the pathophysiology of diphtheria?

Diphtheria toxin is an exotoxin secreted by Corynebacterium, the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophage called corynephage β. The toxin causes the disease in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis.

Is diphtheria a serious disease?

Diphtheria is a serious infection caused by strains of bacteria called Corynebacterium diphtheriae that make toxin (poison). It can lead to difficulty breathing, heart failure, paralysis, and even death. CDC recommends vaccines for infants, children, teens, and adults to prevent diphtheria.

What is the molecular weight of diphtheria toxin?

Diphtheria toxin (DT) is synthesized by certain strains of Corynebacterium diphtheriae and secreted as an inactive proenzyme, composed of a single polypeptide chain having an approximate molecular weight of 58 kDa.

What type of toxin is diphtheria toxin?

Diphtheria toxin belongs to the so-called bifunctional A–B toxins (Figure 2-10). Portion A mediates the enzymatic activity responsible for halting protein synthesis in the target cell while portion B binds to a cell receptor and mediates the translocation of the A chain into the cytosol.

What are examples of AB toxins?

Botulinum toxins are members of a broad class of bacterial toxic proteins, called AB toxins. These are secreted bacterial proteins that enter cells and exert their toxic effects by affecting intracellular processes. Other AB toxins include tetanus, cholera, anthrax, shiga and diphtheria toxins.

Which type of bacteria produces an A-B toxin?

Anthrax Toxin Anthrax is an AB enterotoxin produced by the Gram positive bacteria, Bacillus anthracis.

Which toxin is produced in diphtheria?

Diphtheria toxin (DT) is an extracellular protein of Corynebacterium diphtheriae that inhibits protein synthesis and kills susceptible cells. The gene that encodes DT (tox) is present in some corynephages, and DT is only produced by C. diphtheriae isolates that harbor tox+ phages.

Why diphtheria toxin is an A-B toxin?

The Diphtheria toxin also is an AB toxin. It inhibits protein synthesis in the host cell through phosphorylation of the eukaryotic elongation factor 2, which is an essential component for protein synthesis.

What are AB toxins quizlet?

AB toxins are two-component protein complexes secreted by pathogenic bacteria. Two types: 1) Single precursor protein (one gene) is cleaved into A and B subunits that remain covalently associated (e.g. tetanus toxin)

What is A-B toxin produced by?

bacteriaA-B Toxins are intentionally produced by bacteria to modify host organisms, such as ourselves. They consistent two protein components or subunits, one that causes the effect, and the other which causes the exotoxin to be internalized by body cells so as to cause that effect.

Is cholera an A-B toxin?

Cholera toxin, by acting as a classical A-B type toxin, leads to ADP-ribosylation of G protein, and constitutive activation of AC, thereby giving rise to increased levels of cyclic AMP within the host cell (Fig. 1).

Which type of bacterium produces an A-B toxin quizlet?

A-B exotoxin that affect nerve impulse transmission. Produced by Clostridium tetani and Clostridium botulinum.

What are the 5 types of diphtheria?

Respiratory and cutaneous diphtheria are caused by toxic strains of the bacteria Corynebacterium diphtheriae and Corynebacterium ulcerans and very rarely Corynebacterium pseudotuberculosis....Diphtheriaclassical respiratory diphtheria.laryngeal diphtheria.nasal diphtheria and.cutaneous diphtheria (skin lesions).

What is the most common type of diphtheria?

Classical respiratory diphtheria: The most common type of diphtheria, classical respiratory diphtheria may affect your nose, throat, tonsils or larynx (voice box). Symptoms can vary depending on where the affected membranes are located in your body.

What is diphtheria toxoid?

Diphtheria toxoid is a purified preparation of inactivated diphtheria toxin. It is highly effective in inducing antibodies that will prevent disease, although antibodies may not prevent acquisition or carriage of the organism.

What are AB exotoxins?

0:081:13A B Exotoxins Diphtheria Exotoxin - Microbiology animations - YouTubeYouTubeStart of suggested clipEnd of suggested clipA bee toxins are proteins that consists of two parts a and B the a portion is an enzyme thatMoreA bee toxins are proteins that consists of two parts a and B the a portion is an enzyme that constitutes the toxic part the B portion binds to host cell receptors.

What is A-B toxin produced by?

bacteriaA-B Toxins are intentionally produced by bacteria to modify host organisms, such as ourselves. They consistent two protein components or subunits, one that causes the effect, and the other which causes the exotoxin to be internalized by body cells so as to cause that effect.

Are AB toxins exotoxins?

Examples of A-B toxins include: Diphtheria exotoxin, produced by Corynebacterium diphtheriae (inf). This toxin interferes with host cell protein synthesis by catalyzing the ADP-ribosylation of host cell elongation factor 2 (EF-2), necessary in order for tRNA to insert new amino acids into the growing protein chain.

Is botulinum toxin an A-B toxin?

AB toxins are a family of bacterial toxins that include diphtheria toxin, cholera toxin, anthrax toxin, Shiga toxin, and botulinum toxin, among others [5,6,7,8,9].

Which domain binds diphtheria toxin?

Diphtheria toxin receptor binds diphtheria toxin at the EGF-like domain, and this domain is sufficient to bind diphtheria toxin, while binding of heparin-like molecules to HBD is necessary for full binding activity of diphtheria toxin receptor to diphtheria toxin when assayed in intact cells (Shishido et al., 1995 ).

What is the secretion site of Diphtheria?

Diphtheria toxin is secreted from Corynebacterium diphtheriae as a single polypeptide chain containing two major domains: DT-A, which carries the active site for ADP ribosylation of EF-2, and DT-B, which promotes binding of toxin to cells and the entry of the A chain into the cytosolic compartment.

What is DT in humans?

Diphtheria toxin (DT) is a protein produced by Corynaebacteria diphtheriae. It binds to the heparin-binding epithelial growth factor receptor (EGFR) in human cells enabling its endocytosis and entry to the cytoplasm of subunit A (DTA), where it binds to and inactivates the ribosomal protein eEF-2, disabling the translational machinery which triggers apoptotic cell death rapidly. In humans, whooping cough, a disease of the upper respiratory tract caused by C. diphtheriae, frequently results in lethality owing to release of toxin in the upper respiratory tract and circulatory delivery to the myocardium and other vital organs. One milligram of purified DT is lethal to humans. Rodents, including mice, however, have a form of EGFR that does not bind DT and are therefore completely resistant to the toxic effects of extracellular DT [30] ( Fig. 3.3 ). Transgenic expression of the catalytically active subunit DTA intracellularly has been used by molecular biologists in cellular ablation [31–34]. Initially this technique was used to delete stem cells that had not incorporated a transgene faithfully, but transgenic expression of DTA under a cell-specific promoter leads to ablation of any cell that transcribes the transgene. Similarly, transgenic expression of the human heparin-binding EGFR, which is the diphtheria toxin receptor (DTR), in mouse cells, renders those cells susceptible, like human cells, to extracellular exposure of DT [35]. Transgenic expression of DTR selectively in one of a restricted number of cell types can yield a mouse in which injection of DT into the circulation results in uptake of the DTA subunit only into cells expressing the transgene and rapid loss or ablation of the specific cell-type [30,36–39]. The use of these systems was first reported by Evans in 1989, and Breitman in 1990 [33,40,41]. However, one of the first successful uses of this model system in mice was reported by Lang and Bishop in 1993 [42]. In these studies expression of DTA was transgenically driven by a promoter created by the fusion of a portion of a viral promoter and part of the granulocyte–macrophage colony-stimulating factor (GM-CSF). This resulted in restricted expression of the transgene only in macrophages in the peritoneal cavity and the eye, and also inflammatory macrophages and these populations of macrophages were absent. The resultant surviving mice carried a very distinctive phenotype, in the eye. The hyaloid microvasculature of the developing eye, which normally regresses following delivery of newborns, failed to regress in the absence of macrophages in the eye ( Fig. 3.4 ). This novel method was the first genetic system to study macrophage function in vivo by cellular ablation and showed that a major function of macrophages is in tissue remodeling.

What is DT in a cell?

Diphtheria toxin (DT) is together with CT the best studied enterotoxin with regard to its structure and function. DT is a 58-kDa protein produced as a single polypeptide by lysogenic Corynebacterium diphtheriae strains. After reduction of disulfide bonds, DT consists of two fragments, A and B, responsible for enzymictoxic and cell-binding properties, respectively ( Van Ness et al., 1980; Bennett et al., 1994 ). Like the previous toxins discussed, DT ADP-ribosylates an intracellular target protein, for DT the elongation factor 2, which thereby becomes inactive, resulting in inhibition of cellular protein synthesis and cell death.

What is the amino acid residue of EF-2 that is ADP-ribosylated by diph?

The amino acid residue of EF-2 that is ADP-ribosylated by diphtheria toxin is a posttranslationally modified histidine called diphthamide. The diphthamide residue is unique to EF-2 from eukaryotes and Archea and is not found in any other protein ( Bodley et al., 1984; Collier, 2001 ).

What is DT in biology?

Diphtheria toxin ( DT) is one of the most studied molecules, demonstrating compelling activity as a suicide gene therapeutic reagent. It efficiently ADP-ribosylates elongation factor-2 (EF-2) and thus blocks the translational machinery of target cells.

What is fusion toxin?

Targeted fusion toxins consist of a targeted protein such as a growth factor fused to a bacterial toxin such as diphtheria toxin. The fused toxin is directed to the tumor cells via the targeting molecule, directed into the cells through receptor endocytosis, and then the toxin is released, resulting in tumor cell death.

How many helices are in the catalytic domain of diphtheria toxin?

The crystal structure of diphtheria toxin, along with the use of experimental data, allowed for the separation of the polypeptide chain into three distinct domains ( Figure 9 (a) ). 95,96 The catalytic domain is composed of eight β strands and seven α helices, and it contains the active site required for the toxins activity in inhibiting protein synthesis. The translocation domain, as in the case of colicins, is formed by 10 α helices packed together in a globular domain ( Figure 9 (b) ). The third domain of the protein is the receptor binding domain, which presents a globular β-sheet-rich fold. As for colicins, membrane insertion is thought to be triggered by acidic pH, 94 with the translocation domain adopting a molten globule fold followed by insertion of the hydrophobic central α helices into the membrane. 97,98 In the case of membrane interaction of diphtheria toxin, two conformations have been described – a shallow inserted state and a deep inserted state. In the shallow inserted state, the helices of the translocation domain are located near the membrane surface, whereas in the deep inserted state, the hydrophobic helices penetrate the membrane. 98 It has been proposed that partially unfolded proteins (molten globule-like conformations), 99 particularly the catalytic domain of the protein, bind to and convert the translocation domain from its shallow inserted state to its deep inserted state, suggesting a tight connection between the C domain and the T domain interactions and protein insertion in the membrane. The nature of the pore-forming structure is still under debate, with both monomeric and oligomeric structures proposed to take part in the formation of the translocation pore. 100

What is DtxR in bacteria?

DtxR (diphtheria toxin repressor ) is an iron-dependent, negative regulator of diphtheria toxin production and iron uptake in Corynebacterium diphtheriae (for a review on DtxR, see Tao et al., 1994 ). It is activated in vitro by divalent metal ions including Fe (II), Cd (II), Co (II), Mn (II), Ni (II), and Zn (II) ( Schmitt and Holmes, 1993 ). DtxR has been reported to have limited homology to Fur (25% similarity at the amino acid level; Boyd et al., 1990 ); however, a BLAST search ( Altschul et al., 1990) with DtxR does not identify Fur as having any significant similarity to DtxR. Although neither protein can substitute for the other ( Boyd et al., 1990), there are many similarities between Fur and DtxR, suggesting that they may be functional homologs, carrying out similar functions inside cells. They both have N-terminal, DNA-binding domains that show structural similarity to the Cap/LexA family of regulatory proteins, and they both function with metals as corepressors to control similar classes of genes.

What is DT in a cell?

Diphtheria toxin (DT) is one of the most extensively studied bacterial toxins with intracellular action. It is produced by toxigenic strains of Corynebacterium diphtheriae and is responsible for the symptoms of diphtheria. The toxin was isolated in 1888. A vaccine was developed in 1923. The crystal structure of the toxin was solved in 1992, bringing tremendous progress in understanding the molecular events involved in toxicity. DT contains three structural domains, each carrying a distinct biological function implicated in the intoxication of the cell: cell-surface binding and internalization into endosomes, crossing of the endosome membrane into the cytosol and blocking of cellular protein synthesis. All three domains of the DT, isolated or combined with other proteins, are now exploited for their biological properties to design biotechnological tools and therapeutics.

What enzyme catalyzes the transfer of adenosine diphosphate ribose?

Diphtheria toxin (an oncolytic enzyme still in the experimental stage), catalyzes transfer of the adenosine diphosphate ribose (ADP-ribose) moiety of nicotinamide adenine dinucleotide (NAD) to elongation factor 2. This enzyme halts protein synthesis. The protein synthesis in tumor cells is 100–10,000 times more sensitive to this toxin than the analogous process in normal cells.

What is DT in a bacterial system?

Diphtheria toxin (DT) is one of the most extensively studied bacterial toxins with intracellular action.

How does DT work?

Diphtheria toxin (DT) functions like other toxins by inhibiting protein synthesis either by modifying elongation factor-2 (EF2) or by acting directly on the ribosome (Siegall, 1994). Most toxins are polypeptide chains with several domains that include a cell recognition chain that attaches to cell surface receptors on the target tumor; a translocation domain that enables the toxin to cross the cell membrane and enter the cell; and an inactivation chain that blocks an important intracellular function leading to cell death (Rustamzadeh et al., 2003; Pastan et al., 2006). After the toxin binds to the overexpressed antigens or receptors on cancer cells, it is endocytosed into the cell and transferred by an endosome to a lysosome or to the Golgi apparatus. The toxin is then separated from the carrier ligand allowing it to inhibit protein synthesis. Toxins can inactivate over 200 EF2s per minute (Figure 15.1 ). Compared to conventional chemotherapy where 10 5 molecules are needed to kill one cell, a single toxin molecule can kill a cancer cell ( Siegall, 1994 ).

How many disulfide bonds are there in DT?

Diphtheria Toxin. DT is synthesized as a single polypeptide that includes two disulfide bonds. It is exported by the bacterial cell via the general secretory pathway as a proenzyme of 63 kDa that must be both cleaved and reduced in order for toxicity to be manifest.

Where is diphtheria most common?

Anyone who travels to an area where diphtheria infections are more common. Diphtheria rarely occurs in the United States and Western Europe, where children have been vaccinated against the condition for decades. However, diphtheria is still common in developing countries where vaccination rates are low.

How to transfer diphtheria?

You can also transfer diphtheria-causing bacteria by touching an infected wound.

What are the symptoms of diphtheria?

Left untreated, diphtheria can lead to: 1 Breathing problems. Diphtheria-causing bacteria may produce a toxin. This toxin damages tissue in the immediate area of infection — usually, the nose and throat. At that site, the infection produces a tough, gray-colored membrane composed of dead cells, bacteria and other substances. This membrane can obstruct breathing. 2 Heart damage. The diphtheria toxin may spread through your bloodstream and damage other tissues in your body, such as your heart muscle, causing such complications as inflammation of the heart muscle (myocarditis). Heart damage from myocarditis may be slight or severe. At its worst, myocarditis can lead to congestive heart failure and sudden death. 3 Nerve damage. The toxin can also cause nerve damage. Typical targets are nerves to the throat, where poor nerve conduction may cause difficulty swallowing. Nerves to the arms and legs also may become inflamed, causing muscle weakness.#N#If the diphtheria toxin damages the nerves that help control muscles used in breathing, these muscles may become paralyzed. At that point, you might need mechanical assistance to breathe.

How long does it take for diphtheria to show up?

Symptoms. Diphtheria signs and symptoms usually begin two to five days after a person becomes infected and may include: A thick, gray membrane covering your throat and tonsils. A sore throat and hoarseness. Swollen glands (enlarged lymph nodes) in your neck.

What happens if you breathe with diphtheria?

If the diphtheria toxin damages the nerves that help control muscles used in breathing, these muscles may become paralyzed. At that point, you might need mechanical assistance to breathe.

What to do if your child has been exposed to someone with diphtheria?

Call your family doctor immediately if you or your child has been exposed to someone with diphtheria. If you're not sure whether your child has been vaccinated against diphtheria, schedule an appointment. Make sure your own vaccinations are current.

Why are people called carriers of diphtheria?

They’re called carriers because they can spread the infection without being sick themselves.

What is an AB toxins?

AB toxin. The AB toxins are two-component protein complexes secreted by a number of pathogenic bacteria. They can be classified as Type III toxins because they interfere with internal cell function. They are named AB toxins due to their components: the "A" component is usually the "active" portion, and the "B" component is usually ...

Why are AB toxins classified as Type III?

They can be classified as Type III toxins because they interfere with internal cell function.

What are some examples of AB toxins?

Examples of the "A" component of an AB toxin include C. perfringens iota toxin Ia, C. botulinum C2 toxin CI, and Clostridium difficile ADP-ribosyltransferase. Other homologous proteins have been found in Clostridium spiroforme. An example of the B component of an AB toxin is Bacillus anthracis protective antigen (PA) protein, B.

What are the B components of AB toxin?

An example of the B component of an AB toxin is Bacillus anthracis protective antigen (PA) protein, B. anthracis secretes three toxin factors: the protective antigen (PA); the oedema factor (EF); and the lethal factor (LF). Each is a thermolabile protein of ~80kDa.

What is the purpose of AB toxin?

The two-phase mechanism of action of AB toxins is of particular interest in cancer therapy research. The general idea is to modify the B component of existing toxins to selectively bind to malignant cells.

What is the A/B subunit?

These proteins consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component (A) enters the cell through endosomes produced by the oligomeric binding/translocation protein (B), and prevents actin polymerisation through ADP-ribosylation of monomeric G-actin. Examples of the "A" component of an AB toxin ...

Is diphtheria an AB toxin?

The Diphtheria toxin also is an AB toxin. It inhibits protein synthesis in the host cell through phosphorylation of the eukaryotic elongation factor 2, which is an essential component for protein synthesis. The exotoxin A of Pseudomonas aeruginosa is another example of an AB toxin that targets the eukaryotic elongation factor 2.

What is the DT in bacteria?

Diphtheria toxin (DT) is synthesized by certain strains of Corynebacterium diphtheriae and secreted as an inactive proenzyme, composed of a single polypeptide chain having an approximate molecular weight of 58 kDa. DT enzymatic activity is expressed when the proenzyme is nicked into two fragments, A and B, linked by a disulfide bond, then reduced with thiols releasing the N-terminal A fragment (molecular weight 21 kDa). The C-terminal B fragment (molecular weight 37 kDa) has no apparent enzymatic activity but is required for toxicity. Evidence suggests that the B fragment is responsible for recognizing and binding the toxin to cell surface receptors.

What is the role of the B fragment in the eukaryotic toxin?

Evidence suggests that the B fragment is responsible for recognizing and binding the toxin to cell surface receptors . Diphtheria toxin catalyzes the ADP-ribosylation of eukaryotic aminoacyl-transferase II (EF-2) using NAD as a substrate, the basis for its toxicity toward eukaryotic organisms.

What is a DTd?

Diphtheria toxoid (DTd) is prepared by formaldehyde inactivation of purified diphtheria toxin. Inactivated bacterial toxins, including DTd, are widely used as protein carriers chemically conjugated to oligosaccarides in licensed vaccines, which induce a more robust immune response against the carbohydrate.

Which transcription factor is activated downstream of the Interleukin-2 receptor?

Activation of the STAT5 transcription factor downstream of the Interleukin-2 receptor (IL-2R) induce....

Overview

Symptoms

Causes

Risk Factors

Complications

• Left untreated, diphtheria can lead to: 1. Breathing problems.Diphtheria-causing bacteria may produce a toxin. This toxin damages tissue in the immediate area of infection — usually, the nose and throat. At that site, the infection produces a tough, gray membrane made up of dead cells, bacteria and other substances. This membrane can obstruct breat...

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