Bacterial toxins inactivation

A subfamily of Rho proteins, the Rnd family of small GTPases, are always GTP-bound and seem to be regulated by expression and localization rather than by nucleotide exchange and hydrolysis. Many Rho GTPase effectors have been identified, including protein and lipid kinases, phospholipase D and numerous adaptor proteins. One of the best characterized effector of RhoA is Rho kinase, which phosphorylates and inactivates myosin phosphatase thereby RhoA causes activation of actomyosin complexes. Rho proteins are preferred targets of bacterial protein toxins ( bacterial toxins). 

Free formalin. Inactivation of bacterial toxins with formalin may lead to the presence of small amounts of tree formalin in the final product. The concentration, as estimated by colour development with acetylacetone, must not exceed 0.02%. 

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

Toxoids are inactivated bacterial toxins. They retain the ability to stimulate the formation of antitoxin, which are antibodies directed against the bacterial toxin. Adjuvants are inert substances, such as aluminum salts (i.e., alum), which enhance vaccine antigenicity by prolonging antigen absorption. 

Another example that can be included in the subunit vaccine class is the use of bacterial toxoids. Many bacteria produce toxins which play an important role in the development of the disease caused by a particular organism. Thus, vaccines against some agents, for example tetanus and diphtheria, consist of the toxin inactivated with formaldehyde conjugated to an adjuvant. Immunization protects from disease by stimulating antitoxin antibody which neutralizes the effects of the toxin. 

A vaccine consists of a suspension of live (attenuated) or killed (inactivated) microorganisms (in whole or fractions), whereas a toxoid is a detoxified bacterial toxin that has the ability to trigger the production of antitoxin once administered into the body. 

Highly potent bacterial toxins such as ricin and diphtheria can completely inhibit cellular protein synthesis at very low levels [26]. The bacterial toxin exerts cytotoxicity through enzymatic inactivation of factors essential for protein synthesis (e.g., riboso-mal RNA, elongation factor 2 or EF2). Inactivation of these proteins, which are... 

In the early 20th century it was recognized that some components of a microbacterial cell were more important than others for protection and thus came the concept of subunit vaccines. When combined with the discovery that bacterial toxins could be inactivated with formaldehyde, the result was the introduction of a diphtheria subunit vaccine in 1923 and a tetanus subunit vaccine in 1927. 

The importance of the Shine-Dalgarno sequence is underscored by the action of the bacterial toxin colecin E3. This toxin inactivates the small subunit of the prokaryotic ribosome by cleavage of about 50 residues from the 3 terminus of 16S rRNA. The cleavage disrupts the sequence that is complementary to the Shine-Dalgarno sequence and thus specifically inhibits the initiation process. Because of the fundamental differences between prokaryotic and eukaryotic initiation just described, colecin E3 does not inhibit the eukaryotic ribosome. 

Monoclonal antibodies produced using this technology are now common tools in research because of their very high specificity. For example, they can be used to locate particular molecules within cells or particular amino acid sequences within proteins. If they are first bound to an insoluble matrix, they are also extremely useful for binding to and hence purifying the particular molecule from crude cell extracts or fractions (see Topic D5). They are also increasingly of use in medicine, both for diagnosis and as therapeutic tools, for example to inactivate bacterial toxins and to treat certain forms of cancer. 

A group of plant lectins, such as abrin, ricin, and mod-eccin, are highly toxic to eukaryotic cells. Their mode of action consists of inhibition of protein synthesis by enzymatically inactivating the EF-2 binding region of the 60S ribosomal subunit, whereas the diphtheria toxin inactivates the EF-2 protein itself. Ricin is isolated from castor beans and has a molecular weight of 66,000. Like most plant and bacterial toxic proteins, ricin contains two... 

In some cases, solubilization of physiologically active materials enhances their potency in other cases, it diminishes their potency. Moreover, the use of surfactants in preparations that are ingested by organisms may increase their solubilization of other physiologically active undesirable materials, such as bacterial toxins or carcinogens. Solubilization may also inactivate preservatives in pharmaceutical preparations by incorporating the former into the micelles of surfactants used in the formulation. 

A bacterial toxin, hormone, or a mineral poison may be Inactivated by adsorption. Ferric hydroxide, a good adsorbent is often used as an antidote in cases of poisoning by arsenic. Gas masks are devices containing an adsorbent or a series of adsorbents which purify the air for breathing by adsorbing the poisonous gases and vapours from the atmosphere. 

Traditional vaccines mainly consisted of live attenuated pathogens, whole inactivated orj nisms, or inactivated bacterial toxins. Many traditional vaccines based on pathogen whole cells often contain components that can cause toxicity related side effects. As a result... 

Fig. 3.3 shows the principle behind the design of immunotoxins. A number of protein toxins of bacterial and plant origin are useful for the production of immunotoxins. These include the diphtheria toxin and pseudomonas exotoxin from bacteria, and ricin, arbin, pokeweed antiviral proteins, saporin, and gelonin from plants (Pastan et al, 1986 Pastan and FitzGerald, 1991). All of these toxins kill cells by entering the cells, and enzymatically inactivating the translational machinery of the cells. Some, such as diphtheria toxin, arbin, and ricin, are composed of two protein chains, A and B. The B chains bind to the cell-surface... 

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