Diphtheria toxin tissue

There is now a substantial literature on the synthesis and testing of chimeric molecules. These substances are each composed of at least two functional domains, such as a tissue-targeting domain and a pharmacologically active domain. One common strategy in constructing chimeric toxins is to isolate the binding domain of one toxin (e.g., diphtheria toxin) and attach this to the poisoning domain of another (e.g., ricin). This chimeric molecule attaches only to cells that have the diphtheria toxin receptor, and it expresses only the intracellular effects of ricin. 

The actions of diphtheria and pertussis toxins are also mediated by ADP-ribosylation. Diphtheria toxin inhibits eukaryotic protein synthesis by ADP ribosylation of elongation factor II (Chapter 23). Pertussis toxin inactivates Gi by ADP ribosylation of its A-subunit and causes an increase in cAMP production. Unlike cholera toxin, pertussis and diphtheria toxins gain access to many tissues to produce diverse biological effects. Severe watery diarrhea... 

Many toxins interfere with intracellular functions. The best-characterized of these are diphtheria toxin and cholera toxin, produced by the bacteria Corynebacterium diptheriae and Vibrio cholerae, respectively. Both of these toxins contain two subunits, called A and B. The A subunit is responsible for the toxic effect, whereas the B subunit binds to the target cell. Once diphtheria toxin has entered the target cell, the A and B subunits split apart. The A subunit, which is an enzyme, catalyzes a reaction that prevents protein synthesis. The cell dies because it cannot synthesize proteins. The host organisms dies because cardiac, kidney, and nervous tissue are destroyed. 

The nature of the primary injury to tissues of susceptible animals caused by botulinus, tetanus, and diphtheria toxins is a problem of fundamental biological importance about which almost nothing is known. 

Diphtheria toxin, which is considerably less toxic than either tetanus or botulinus toxins, seems to be less specific in its action and is capable of causing damage to almost any tissue or organ in the susceptible animal. 

In addition to the classical exotoxins, which damage tissues of susceptible animals in concentrations approximating one molecule per cell, many bacteria excrete extracellular enzymes during their growth which may be more or less toxic. Although none of these extracellular enzymes has been isolated in pure form as yet, it appears probable that their toxic dose is relatively large and the latent period of their action relatively short as compared with tetanus, botulinus, or diphtheria toxins. 

Further work on the nature of diphtheria toxin suggests that this toxin may be the protein moiety of diphtherial cytochrome b (155, 156). Cytochrome b is present in relatively high concentration in diphtheria bacilli grown on media containing an excess of iron and is concerned in the oxidation of succinate by bacterial extracts. It has been suggested that the toxin may act by interfering with the function of cytochrome b in the tissues of susceptible animals, possibly by blocking its synthesis. 

This is an acute, non-invasive infectious disease associated with the upper respiratory tract (Chapter 4). The incubation period is fiom 2 to 5 days although the disease remains communicable for up to 4 weeks. A low molecular weight toxin is produced which affects myocardium, nervous and adrenal tissues. Death results in 3-5% of infected children. Diphtheria immunization protects by stimulating the production of an antitoxin. This antitoxin will protect against the disease but not against infection of the respiratory... 

A-B Toxins are bacterial toxins composed of two peptide chains one (B) that binds to the invaded cell surface, and the other (A) containing the toxin which is then taken-up into the cell. Some examples of exotoxins secreted by the bacteria into the surrounding medium and highly toxic to certain tissues are pathogens causing botuiism (Clostridium botulinum), tetanus (Clostridium tetani) and diptheria (Corynebacterium diphtheria. An example of an A-B endotoxin is Vibrio cholerae. Botulinum toxin and tetanus toxin have their main toxic actions on neuronal tissues, so are described at NEUROTOXINS. 

Plants are not the only organisms that produce such environmentally transmittable toxins. A number of different bacterial species produce exotoxins, which are chemicals that, once secreted, act at a site removed from the bacterial growth. Exotoxins are usually proteins that interact with host cells, producing a wide variety of responses, and most exotoxins act at tissue sites remote from the bacteria that produce them. Many of these exotoxins cause disease, and some well-known and historically devastating diseases, such as botulism, diphtheria, and tetanus, are caused not by the bacteria themselves but rather by the exotoxins that they secrete. A perfect example of this phenomenon are the neurotoxins produced by the bacteria Clostridium botulinum. 

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