Exotoxin

Materials produced by crystalliferous bacilli which elicit a toxic response in susceptible insects may be separated into two types. The first type, the true toxins, include the crystalline protein inclusion body the parasporal body of Hannay (14)], a heat-stable, water-soluble exotoxin active against flies, a heat-stable, dialyzable water-soluble exotoxin, toxic to Lepidoptera on injection (23), and a heat-labile, water-soluble, filterable exotoxin, toxic toward larch sawfly larvae (Hymenoptera) which was reported by Smirnoff (31). 

Water-Soluble Exotoxins. In this area, we enter into the slightly muddy waters of the lower molecular weight compounds which elicit toxic responses in susceptible host insects. Without reference to molecular identity, it is possible to sift through the various reports on the effects of bacillus-produced soluble exotoxins and recognize three possible types of material which are produced under appropriate conditions by specific strains of bacilli ... 

The exotoxin reported by Smirnoff (31) is definitively different from other soluble toxins, as indicated by its reported heat lability. This soluble toxin was obtained from the supernatant of a sporulated B. thuringiensis culture. In testing, it was found to be very toxic by ingestion to 18 species of larch sawfly larvae. No further studies on this toxin have been reported at this time. 

Bacterial Toxins. Table 1 Intracellular acting exotoxins... 

Diphtheria toxin, Pseudomonas exotoxin A Elongation factor 2 ADP-ribosylation Inhibition of protein synthesis (diphtheria, Pseudomonas infection)... 

Pasteurella multocida toxin (PMT) is the major pathogenic factor responsible for atrophic rhinitis, a disease which is characterized by bone loss in the nose of pigs. PMT is a 145 kDa single-chain exotoxin, which activates Goq protein (but not Gan) and stimulates phospholipase C 3. In addition, G12/i3 proteins and subsequently Rho pathways are activated. 

Gram-positive (whole organisms peptidoglycans [e.g., muramyl dipeptide] lipoteichoic acids exotoxins enterotoxins erythrogenic toxins group B polysaccharides)... 

Diphtheria toxin, an exotoxin of Corynebacterium diphtheriae infected with a specific lysogenic phage, catalyzes the ADP-ribosylation of EF-2 on the unique amino acid diphthamide in mammalian cells. This modification inactivates EF-2 and thereby specifically inhibits mammalian protein synthesis. Many animals (eg, mice) are resistant to diphtheria toxin. This resistance is due to inability of diphtheria toxin to cross the cell membrane rather than to insensitivity of mouse EF-2 to diphtheria toxin-catalyzed ADP-ribosylation by NAD. 

Particular strains of salmonellae (section 4.2) such as Sal. typhi, Sal. paratyphi and Sal. typhimurium are able not only to penetrate into intestinal epithelial cells and produce exotoxins but also to penetrate beyond into subepithelial tissues. These organisms therefore produce, in addition to the usual symptoms of salmonellosis, a characteristic systemic disease (typhoid and enteric fever). Following recovery frxm such infection the organism is commonly found associated with the gall bladder, hi this state, the recovered person will excrete the organism and form a reservoir for the infection of others. 

Damage to the host may arise in two ways. First, multiplication of the microorganisms may cause mechanical damage to the tissue cells through interference with the normal cell metabolism, as seen in viral and some bacterial infections. Second, a toxin associated with the microorganism may adversely affect the tissues or organs of the host. Two types of toxins, called exotoxins and endotoxins, are associated with bacteria. 

The second B. thuringiensis toxin, the /3-exotoxin has a much broader spectrum encompassing the Lepidoptera, Coleoptera and Diptera. It is an adenine nucleotide, probably an ATP analogue which acts by competitively inhibiting enzymes which catalyse the hydrolysis of ATP and pyrophosphate. This compound, however, is toxic when administered to mammals so that commercial preparations of the B. thuringiensis 5-endotoxin are obtained from strains which do not produce the j8-exotoxin. 

Diphtheria is a bacterial respiratory infection characterized by membranous pharyngitis. The membrane may cover the pharynx, tonsillar areas, soft palate, and uvula. Diphtheria may also cause anal, cutaneous, vaginal, and conjunctival infections. The impact of diphtheria is not from the causative bacteria, Corynebacterium diphtheriae, but rather from complications attributed to its exotoxin, such as myocarditis and peripheral... 

TRIGGERING MOLECULES (endotoxins, exotoxins, teichoic acid, etc.)... 

Bjorn, M.J., Croetsema, G., and Scalapino, L. (1986) Antibody-Pseudomonas exotoxin A conjugates cytotoxic to human breast cancer cells in vitro. Cancer Res. 46, 3262. 

Infections can damage nerves directly, or via exotoxins 621 Antibody- and cell-mediated mechanisms of neuropathy 621 Immune mechanisms contribute to paraneoplastic neuropathies 623 Toxins and hormone deficiency states are frequent causes of neuropathy 623 Many genetically determined neuropathies are now recognized 624 Neurofibromatosis is a frequent cause of peripheral nerve tumors 625... 

Diphtheria causes a demyelinative neuropathy. Coryne-bacterium diphtheriae colonizes the pharynx or open wounds, and secretes a protein exotoxin. The B subunit of this exotoxin binds to plasma membranes and facilitates entry into cytosol of the A subunit, which catalyzes ADP-ribosylation, and inactivation of an elongation factor required for protein synthesis. Cardiac muscle and Schwann cells are particularly susceptible to this toxin, and hence patients with diphtheria develop cardiomyopathy and demyelinative polyneuropathy [20]. While diphtheria is now uncommon because of childhood immunization against C. diphtheriae, the disruption in preventative medicine programs caused by disintegration of the Soviet Union was followed by a substantial incidence of diphtheritic polyneuropathy in Russia. 

Botulinum exotoxin impedes release of neurotransmitter vesicles from cholinergic terminals at neuromuscular junctions. Botulinum exotoxin is ingested with food or, in infants, synthesized in situ by anaerobic bacteria that colonize the gut. A characteristic feature of botulinum paralysis is that the maximal force of muscle contraction increases when motor nerve electrical stimulation is repeated at low frequency, a phenomenon attributable to the recruitment of additional cholinergic vesicles with repetitive depolarization of neuromuscular presynaptic terminals. Local administration of Clostridium botulinum exotoxin is now in vogue for its cosmetic effects and is used for relief of spasticity in dystonia and cerebral palsy [21]. 

Exotoxin A toxin secreted by a microorganism into the surrounding medicine. 

A rigorous structural proof of the insecticidal exotoxin (34) from Bacillus thurin-giensis has now been published,107 confirming the a-configuration of the glucosidic bond. The total synthesis of (34) is further confirmation of the correctness of the structural assignment.108 The exotoxin inhibits RNA synthesis in insects and animals and affects the incorporation of orotic acid into nuclear RNA.109... 

A r-(3-oxododccanoyl)-L-homoscrinc lactone, OdDHL or 30, C12-HSL Pseudomonas aeruginosa Virulence factors - alkaline protease, clatasc, exotoxin A, haemolysin, neuraminidase, exoenzyme S, Xcp secretion, RhlR, biofilm formation. 

In contrast to Gram-negatives, many Gram-positive bacteria employ post-translationally modified peptides processed from larger precursors as QS signal molecules. In Staphylococcus aureus, for example, a family of peptide (7-9 amino acid residues) thiolactones which vary in the primary amino acid sequence but contain a conserved cysteine at position 5 control the expression of cell wall colonization factors and exotoxins [24-26]. 

Very recently the protein structures of ACE with the bound inhibitors Lisinopril (Fig. 4) and Captopril were published (101,102). Also the protein structure of the LF from Bacillus anthracis (PDB-Code 1J7N) caused a sensation, which is now available to the public (Fig. 14b) (103). LF is part of the toxic exotoxin complex composed of three distinct proteins (protective antigen PA, the lethal factor LF and the edema factor EF), and is thought to be the most toxic... 

Microorganism Activate T Lymphocytes and Bystander Cells in the Skin in Atopic Dermatitis An important strategy by which S. aureus exacerbates atopic dermatitis is by secreting exotoxins. Some of them function as superantigens, which stimulate activation of T cells and major histocompatibility (MHC) class II + APC or keratinocytes, which express MHC class II upon activation. Many effects on T lymphocytes and other cells are elicited by superantigens (table 1). 

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