Clostridial

The above mentioned Rho GTPases are glucosylated by the family of clostridial glucosylating cytotoxins. 

Important members of this toxin family are Clostridium difficile toxins A and B, which are implicated in antibiotics-associated diarrhea and pseudomembranous colitis. The large clostridial cytotoxins are single-chain toxins with molecular masses of 250-308 kDa. The enzyme domain is located at the N terminus. The toxins are taken up from an acidic endosomal compartment. They glucosylate RhoA at Thr37 also, Rac and Cdc42 are substrates. Other members of this toxin family such as Clostridium sordellii lethal toxin possess a different substrate specificity and modify Rac but not Rho. In addition, Ras subfamily proteins (e.g., Ras, Ral, and Rap) are modified. As for C3, they are widely used as tools to study Rho functions [2] [4]. 

Just I, Gerhard R (2004) Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol 152 23-47... 

Clostridial neurotoxins are bacterial protein toxins that consist of a heavy and a light chain connected by a disulfide bond and non-covalent interactions. They... 

The light chains of the clostridial neurotoxins are metalloproteases with exclusive specificity for neuronal SNAREs. TeNT, BoNTs B,D,F, and G cleave synapto-brevin, BoNTs A and E SNAP-25, and BoNT/Cl syntaxin, and to a lesser extent also SNAP-25. Cleavage of any of the SNAREs causes complete and irreversible block of synaptic transmission. 

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. 

Clonal Selection Clostridial Neurotoxins Clostridium Botulinum Toxin Clotting CNTF... 

Methylanaline could be transnitrosated with nitrite and S-nitrosocysteine and also by a simulated protein bound nitrite. In the latter case, an important factor was the local concentration of nitrosothiol groups on the matrix. The effects of S-nitrosocysteine as an inhibitor of lipid oxidation, as a color developer, and as an anticlostridial, have been reported recently in a turkey product (31). The Molar concentration of RSNO equating to 25 ppm nitrite gave similar results for color and inhibition of lipid oxidation but had less anti-clostridial activity. Transnitrosation between RSNO and heme protein was demonstrated. 

Arkowitz RA, RH Abeles (1989) Identification of acetyl phosphate as the product of clostridial glycine reductase evidence for an acyl enzyme intermediate. Biochemistry 28 4639-4644. 

Anke, G. H., Thomas, M., Frank, G., Reiner, S., Helge, B., Markus, K., and Monika, K. (2008). Challenging the problem of clostridial identification with matrix-assisted laser desorption and ionization-time-of-fight mass spectrometry (MALDl-TOF MS). Anaerobe 14, 242-249. 

Another important necrotizing skin and soft tissue infection is clostridial myonecrosis (gas gangrene). Clostridial myonecrosis can develop spontaneously but most often occurs after trauma. Clostridium perfringens is the most common causative pathogen. 

Tens of thousands of Americans, including 1 of every 12 persons with spinal cord injury, die each year as a result of complications relating to pressure sores.41 Most complications are infectious. The most common is osteomyelitis, which is present in approximately 38% of infected pressure sores.37 Less frequently, NF, clostridial myonecrosis, and sepsis can occur. 

Day (1991) cites the case of mastitis in cattle where nosodes, used in preventive programmes, have reduced the incidence of mastitis and have made those cases which do occur easier to clear. Caulophyllum has been used to treat dystokia (calving problems) with success. However, Day (1993) is equally clear as to when a homoeopathic nosode is not advisable. He states that nosodes do exist for the prevention of clostridial diseases in sheep, but they have not been proved to be effective. Some people have used them with apparent success, but there was no evidence as to a significant challenge. 

Although also iron-sulfur proteins, the rubredoxins do not generate H2S on acidification since in this case the thiol groups are contributed by cysteinyl residues in the polypeptide chain. The function of clostridial rubredoxin is as yet unknown in Pseudomonas sp. a similar protein catalyzes the co-hydroxylation of alkanes, a reaction requiring molecular O2. 

Recently Jensen and co-workers have determined the structure of a clostridial-type ferredoxin obtained from Micrococcus aerogenes (47). One of the two apparently identical iron-sulfur clusters is illustrated in Fig. 2. The structure is compatible with a model with iron and labile sulfide at alternate comers of a cube. This accounts for the equivalence of these moieties in the protein. Another 8-iron-8 labile sulfur ferredoxin, from Clostridium acidiurici, similarly contains two independent iron-sulfur clusters per molecule (48). Strahs and Kraut (49) had earlier discovered... 

Kim, J., Darley, D.J., Buckel, W., and Pierik, A.J. 2008. An Allylic ketyl radical intermediate in clostridial amino-acid fermentation. Nature 452 239-242. 

In further work on this series, the same methods were used for the examination of the action pattern of highly purified pectinesterase produced by Fusarium oxysporum f. sp. vasinfectum.49 This pectinesterase was found to affect highly esterifled pectin by a mechanism similar to that of tomato pectinesterase, that is, more than half of the enzymic activity occurred at the reducing ends of the molecules, and the rest attacked a different locus or loci of the pectin chains. These conclusions were supported by a comparison of the effect of clostridial lyase on pectin partly de-esterified in an alkaline solution with its effect on pectin partly de-esterified by Fusarium oxysporum pectinesterase. The lyase did not act on the randomly... 

Binding of PLA2 toxin to the nerve membrane, although selective, is less well understood than that of clostridial... 

Clostridial gas gangrene (myonecrosis) should be treated with clindamycin and penicillin. 

Barth H, Blocker D, Aktories K. The uptake machinery of clostridial actin ADP-ribosylating toxins—a cell delivery system for fusion proteins and polypeptide drugs. Naunyn Schmiedebergs Arch Pharmacol 2002 366(6) 501-512. 

EC1.4.1.2 glutamate dehydrogenase, clostridial NAD -dependent (amino acid dehydrogenase)... 

Classical bacterial exotoxins, such as diphtheria toxin, cholera toxin, clostridial neurotoxins, and the anthrax toxins are enzymes that modify their substrates within the cytosol of mammalian cells. To reach the cytosol, these toxins must first bind to different cell-surface receptors and become subsequently internalized by the cells. To this end, many bacterial exotoxins contain two functionally different domains. The binding (B-) domain binds to a cellular receptor and mediates uptake of the enzymatically active (A-) domain into the cytosol, where the A-domain modifies its specific substrate (see Figure 1). Thus, three important properties characterize the mode of action for any AB-type toxin selectivity, specificity, and potency. Because of their selectivity toward certain cell types and their specificity for cellular substrate molecules, most of the individual exotoxins are associated with a distinct disease. Because of their enzymatic nature, placement of very few A-domain molecules in the cytosol will normally cause a cytopathic effect. Therefore, bacterial AB-type exotoxins which include the potent neurotoxins from Clostridium tetani and C. botulinum are the most toxic substances known today. However, the individual AB-type toxins can greatly vary in terms of subunit composition and enzyme activity (see Table 2). 

In a very different fashion from the clostridial/bacillus binary toxins, S. superantigens such as the SEs... 

Malkin R, Rabinowitz JC. 1966. The reconstitution of clostridial ferredoxins. Biochem Biophys Res Commun 23 822-7. 

Table 12.1 summarizes the selenoenzymes isolated from Clostridia, which fall into three major categories. The first group is the amino acid reductases, such as GR, sarcosine reductase (SR), betaine reductase (BR), and proline reductase (PR). The second class of selenoenzymes includes FDH. Although a number of clostridial species are suspected to contain a... 

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