Diphtheria bacillus

The history of the development of antitoxins in combating bacterial infection dates back to the early beginnings of organized bacteriology. Belrring was tile first to show that animals that were immune to diphtheria contained, in their serum, factors which were capable of neutralizing the poisonous effect of the toxins derived from the diphtheria bacillus. While this work was earned out in 1890, prior to many of the great discoveries of mass immunization, and much later the antibiotics, there yet remains a place for antitoxins in medical treatment or prophylaxis for some diseases, such as tetanus and botulism,... 

R. Minck and A. Minck (1949). Constitution of diphtheria bacillus, nuclear apparatus and metachromatic granulations. C.R. Acad. Sci. Paris, 228, 1313-1315. 

Erythromycin 250 mg four times daily for 7 days is very effective for acute infections or for eradicating the carrier state. The other macrolides also are likely to be effective because clinical experience with them is lacking, they are not FDA approved for this indication. The presence of an antibiotic does not alter the course of an acute infection with the diphtheria bacillus or the risk of complications. Antitoxin is indicated in the treatment of acute infection. 

In this environment, the microbial theory many diseases constituted the hallmark of nineteenth-century medicine. The theory that infectious diseases were caused by invisible agents provided an opportunity for much progress. The laboratory took its rightful place when microscopes, staining of preparations and sterilization became available for new discoveries. For example, Escherichia coli, discovered in 1879, became the perfect example of an easily grown, safe bacteria for laboratory practice. Working with pure cultures of the diphtheria bacillus in the Pasteur Institute, in Paris, Emile Roux (1853-1933) and Alexandre Yersin (1863-1943) first isolated, in 1888, the deadly toxin that causes most of diphtheria s lethal effects. One by one over the next several decades, various diseases revealed their microbial origins. 

Nicotinic acid as a growth accessory for the diphtheria bacillus. J, biol. 

Further suggestive evidence that the carboxylated porphyrins are precursors of protoporphyrin is presented in the studies in C. diphtheriae. It had been shown by Pappenheimer that on low iron the production of porphyrin as well as of diphtheria toxin excreted into the medium was high when the iron content of the medium was increased, both the excretion of porphyrin and the toxin were diminished. Studying the heme and porphyrin pigments of this organism, Rawlinson and Hale observed that on a medium low in iron, the diphtheria bacillus excreted high concentrations of coproporphyrin III at the same time that heme production was diminished. When the iron content of the medium was increased to a level sufficient to inhibit toxin and coproporphyrin production, the intracellular heme components, namely, cytochrome a and b, but not c, rose five- to ten-fold. 

A AL transaminase has been isolated from several tissues by Kowalski et al. (57). From the diphtheria bacillus transaminases for fi-AL a-keto-glutarate and 5-AL pyruvate have been shown by Bagdasarian (58). 

FIGURE 10.32 The structures of (a) S-eudotoxiu (two views) from Bacillus thuringiensis and (b) diphtheria toxin from Cmynehacterium diphtheriae. Each of these toxins possesses a bundle of a-hehces which is presumed to form the trausmembraue channel when the toxin Is Inserted across the host membrane. In S-endotoxln, helix 5 (white) Is surrounded by 6 helices (red) In a 7-hellx bundle. In diphtheria toxin, three hydrophobic helices (white) lie at the center of the transmembrane domain (red). 

Polysaccharides of Corynebacterium diphtheriae yield D-galactose, pentoses and amino sugars on hydrolysis.79 D-Glucose and D-mannose are major hydrolytic products of the polysaccharide of Clostridium perfringens.80 Complete hydrolysis81 of the polysaccharide of the anthrax bacillus yielded acetyl-D-glucosamine and D-galactose. 

Que, Q. and Helmann, J. D. (2000). Manganese homeostasis in Bacillus subtilis is regulated by MntR, a bifunctional regulator related to the diphtheria toxin repressor family of proteins, Mol. Microbiol., 35, 1454-1468. 

Benzylpenicillin or penicillin G has a narrow antimicrobial spectrum. It is active with respect to Gram-positive bacteria (staphylococcus, streptococcus, and pneumococci), causative agent of diphtheria, and anthrax bacillus. Gram-negative bacteria are resistant to it. Benzylpenicillin is broken down by stomach acid and destroyed by staphylococcus penicillinase. 

Among the bacilli, gram positive Bacillus anthracis, Corynebacterium diphtheriae, Clostridium species are highly sensitive. Among the spirochetes. Treponema pallidum is highly sensitive to penicillin. 

Bacillus anthracis Clostridium perfringens Corynebacterium diphtheriae Listeria monocytogenes... 

So far, only two catalytic residues have been identified in SI Glu-129 (Antoine et ai, 1993) and His-35 (Antoine and Locht, 1994). The first residue is conserved in all known ADP-ribosylating toxins, whereas His-35 is only conserved in cholera toxin and a recently identified mosquitocidal toxin produced by Bacillus sphaericus. This residue is not present in diphtheria toxin and exotoxin A (Fig. 1). The absence of this catalytic residue in the latter two toxins may explain their inefficiency in carrying out the NAD -glycohydrolysis reaction, compared to PT and cholera toxin. The acceptor substrate of diphtheria toxin and exotoxin A is diphthamide, a modified histidine residue in EF2. Perhaps this residue may take on some of the functions of the catalytic His residue in the other toxins. 

Bacillus anthracis Bordetella pertussis Clostridium bifermentans Clostridium botulinum Clostridium fallax Clostridium histolyticum Clostridium oedematiens Clostridium septicum Clostridium welchii (perfringens) Corynebacterium diphtheriae Flavobacterium meningosepticum Leptospira icterohaemorrhagiae... 

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