Clostridium inhibition

Small GTPases of the Rho family are ADP-ribosylated (e.g., at Asn4l of RhoA) and inactivated by C3-like toxins from Clostridium botulinum, Clostridium limosum, and Staphylococcus aureus. These proteins have a molecular mass of 23-30 kDa and consist only of the enzyme domain. Specific inhibition of Rho functions (Rho but not Rac or Cdc42 are targets) is the reason why C3 is widely used as a pharmacological tool [2]. 

Another subfamily of ADP-iibosylating toxins modifies G-actin (at Argl77), thereby inhibiting actin polymerization. Members of this family are, for example, C. botulinum C2 toxin and Clostridium perfringens iota toxin. These toxins are binary in structure. They consist of an enzyme component and a separate binding component, which is structurally related to the binding component of anthrax toxin [3]. 

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

Vancomycin (Vancocin) acts against susceptible gram-positive bacteria by inhibiting bacterial cell wall synthesis and increasing cell wall permeability. This drug is used in the treatment of serious gram-positive infections that do not respond to treatment with other anti-infectives. It also may be used in treating anti-infective-associated pseudomembranous colitis caused by Clostridium difficile. 

Similar to catechins, several studies have reported that proanthocyanidins exhibit a more or less pronoimced antibacterial activity. Chimg et al. [76] reported that proanthocyanidins determine the growth inhibition of strains of Aeromonas spp.. Bacillus spp., Clostridium botulinum, Clostridium per-fringens, Enterobacter spp., Klebsiella spp., Proteus spp.. Pseudomonas spp.. Shigella spp., S. aureus. Streptococcus spp., and Vibrio spp. 

It has been postulated that Chlamydia may produce a heat shock protein that causes tissue damage through a delayed hypersensitivity reaction. C. trachomatis may also possess DNA evidence of toxin-like genes that code for high-molecular-weight proteins with structures similar to Clostridium difficile cytotoxins, enabling inhibition of immune activation. This may explain the observation of a chronic C. trachomatis infection in subclinical PID. 

Kim, B. H. Bellows, P. Datta, R., and Zeikus, J. G., Control of carbon and electron flow in Clostridium acetobutylicum fermentations Utilization of carbon monoxide to inhibit hydrogen production and to enhance butanol yields. Appl. Environ. Microbiol., 1984. 48 pp. 764-770. 

Inhibition of ENR FabK is appropriate for either a narrow spectrum against Streptococci and Clostridium difficile since it is an essential target for these species, or a broader spectrum in combination with a FabI inhibitor since some bacteria such as E. faecalis share both isoforms. 

The activity of exopectate lyase of Clostridium multifermentans depends on the presence of bivalent cations of Ca, Ba, Sr, Mg, and Mn. The activation constant with calcium chloride is 0.06 mM. In a later stage of substrate degradation, an inhibition by Ca2+ was observed at concentrations above 0.5 mM this was attributed by Macmillan and Vaughn105 to a binding of calcium to the carboxyl group of two different molecules of substrate and to the inability of exopectate lyase to split the substrate as this barrier is approached. 

Chaddock, J.A., Purkiss, J.R., Friis, L.M., Broadbridge, J.D., Duggan, M.J. Fooks, S.J., Shone, C.C., Quinn, C.P. and Foster, K.A., Inhibition of vesicular secretion in both neuronal and nonneuronal cells by a retargeted endopeptidase derivate of Clostridium botulinum neurotoxin type A, Infect. Immun., 68, 2587-2593, 2000. 

Rodgers, S., Peiris, P. and Casadei, G., Inhibition of nonproteolytic Clostridium botulinum with lactic acid bacteria and their bacteriocins at refrigeration temperatures, J. Food Prot., 66, 674-678, 2003. 

Smith, L.D.S., Inhibition of Clostridium botulinum by strains of Clostridium perfringens isolated from soil, Appl. Microbiol., 30, 319-323, 1975. 

In meat curing, nitrite is traditionally used for developing the pink, heat-stable pigment. Its other important role is the inhibition of the outgrowth of Clostridium botulinum spores in pasteurized products and, in some countries, in several types of smoked fish. Nitrite also serves as an antioxidant and contributes positively to the development of the flavor of cured-meat. The undesirable side-effect, however, is the reaction of nitrite with amino groups of food constituents, leading to the formation of NNCs. 

Dymicky, M. and Huhtanen, C.N. Inhibition of Clostridium botulinumhy p-hydroxybenzoic acid n-alkyl esters, Antimicrob. Agents Chemother, 15 (6) 798-801, 1979. 

Just as too much acetylcholine activity can be a problem, so can too little. Botulinum toxin is a mixture of eight proteins that act to inhibit the release of acetylcholine. This toxin is the product of the anaerobic bacterium Clostridium botulimm. Ingestion of this toxin causes the life-threatening food poisoning known as botulism. 

Figure 3. Kinetics of conq)etitivc inhibition of Clostridium thermohydrosuljur-icum strain 39E purified amylopuUulanase activity with mixed substrates. The solid lines A and C indicate the theoretical plots for competitive inhibition at amylose ccmcentrations of 0.6 and 2.4 mg/ml, respectively. Lines B and D are the theoretical plots for the absence of inhibition at the same respective amylose ccmcentrations. PuUulan was used at concentrations of 0.4, 0.8, 1.2, 1.6, 2.0, 2.4 mg/ml. For clarity, only two sets of data points were used in the above plot. ( ) and (A) are the practical data points obtained at 0.6 and 2.4 mg/ml amylose concentrations. All reaction mixtures contained 5% (v/v) dimethyl sulfoxide for solubility of amylose. [S] = [A] + [P], where S is the total substrate ccmcentration. A and P are the concentrations of amylose and pullulan, respectively. (Reproduced with permissiem from Ref. 13. Copyright 1990 Academic Press, Inc.)...

Lincosamides (lincomycin and clindamycin) are representatives of a very small group of drugs synthesized up of an amino acid bound to an amino sugar. Lincosamides bind with the 50 S ribosomal subunit of bacteria and inhibit protein synthesis. They also inhibit pep-tidyltransferase action. Lincosamides are bacteriostatic antibiotics however, when they reach a certain level in the plasma, they also exhibit bactericidal action against some bacteria. Lincosamides are highly active against anaerobic infections such as Peptococcus, Peptostreptococcus, Actinomyces, Propionibacterium, and Clostridium fringens, a few types of Peptococcus and Clostridium. 

Clindamycin is a chlorine-substituted derivative of lincomycin. However it is more potent and is better absorbed from the gastrointestinal tract and has therefore replaced lincomycin in most situations. Clindamycin is in principle a bacteriostatic agent. Its indications are mainly limited to mixed anaerobic infections. As mentioned above it has a similar mechanism of action as erythromycin. It selectively inhibits bacterial protein synthesis by binding to the same 50s ribosomal subunits. Erythromycin and clindamycin can interfere with each other by competing for this receptor. Also cross-resistance with erythromycin frequently occurs. Resistance is rather chromosomal rather than plasmid mediated and is especially found in cocci and Clostridium difficile. 

Botulism is most commonly caused by ingestion of a neurotoxin produced by Clostridium botulinum in improperly canned food. Poisoning may also occur after wound contamination with the organism. Infant botulism may occur when spores of the organism germinate and manufacture the toxin in the intestinal tract of infants. Botulinum toxin works by inhibiting ACh release at all cholinergic synapses. 

Bacitracin inhibits gram-positive cocci, including Staphylococcus aureus, streptococci, a few gram-negative organisms, and one anaerobe, Clostridium difficile. 

Acetylcholine release is inhibited by one of the most potent toxins, the botulims toxin produced by the anaerobic bacterium Clostridium botulinum. The toxin, lethal at 1 ng/kg in humans, enters the synapse by endocytosis at nonmyelinated synaptic membranes and produces muscle paralysis by blocking the active zone of the presynaptic membrane... 

It is a glycopeptide antibiotic and primarily active against gram positive bacteria, strains of Staph, aureus which are resistant to methicillin are inhibited by vancomycin. It is also effective against Strep, viridans, enterococcus, Clostridium dijficile and diphtheroids. 

Payne, M. j.. Woods, L. F., Gibbs, P., and Cammack, R. (1990). Electron paramagnetic resonance spectroscopic investigation of the inhibition of the phosphoroclastic system of Clostridium sporogenes by nitrite. J. Gen. Microbiol. 136, 2067-2076. 

Reddy, D., Lancaster, J. R., Jr., and Comforth, D. P. (1983). Nitrite inhibition of Clostridium botulinum Electron spin resonance detection of iron-nitric oxide complexes. Science 221, 769-770. 

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