Irreversible Detoxification of Purified Diphtheria Toxin

Scheibel, I.; Christensen, Peter

doi:10.1111/apm.1965.65.1.117

Cited by 10 publications

(4 citation statements)

References 5 publications

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“…The loss of activity caused by Formalin-lysine treatment may be explained by the production of a stabilized molecule unable to undergo such rearrangements due to the formation of interor intramolecular cross-links. Previous studies have demonstrated that diphtheria toxoid produced by Formalin-lysine treatment was far more resistant to toxic reversion than a toxoid produced by treatment with Formalin alone due, in part, to the incorporation of lysine into the toxin molecule (19,30). We obtained similar results with toxin A, suggesting that Formalin-lysine treatment of toxin A resulted in a more stabilized molecule than treatment with Formalin alone.…”

Section: Discussionsupporting

confidence: 77%

Effect of formalin toxoiding on Pseudomonas aeruginosa toxin A: biological, chemical, and immunochemical studies

Cryz

Friedman²,

Pavlovskis

et al. 1981

Infect Immun

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We investigated the effect of Formalin toxoiding on the biological, chemical, and immunological activities of Pseudomonas aeruginosa toxin A. Formalin treatment alone resulted in a 1,000-fold decrease in toxin-induced cell cytotoxicity and altered the antigenicity of the toxin A molecule without adversely affecting enzymatic activity. Competitive blocking experiments indicated that Formalinmediated detoxification proceeded via alterations in a region of the toxin molecule other than the active site of the enzyme. The addition of lysine to Formalin-toxin mixtures not only increased the rate and extent of detoxification and antigenic alteration, but also completely destroyed enzymatic activity. The immunogenicities of different toxoids varied substantially. Upon dialysis and storage, Formalinderived toxoids underwent partial toxic reversion, whereas a Formalin-lysinederived toxoid did not. The sodium dodecyl sulfate-polyacrylamide gel patterns of Formalin-and Formalin-lysine-treated toxins indicated that these treatments caused the formation of a heterogenous group of high-molecular-weight species and produced substantial changes in the electrophoretic mobility of toxin A.

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Section: Discussionsupporting

confidence: 77%

Effect of formalin toxoiding on Pseudomonas aeruginosa toxin A: biological, chemical, and immunochemical studies

Cryz

Friedman²,

Pavlovskis

et al. 1981

Infect Immun

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“…This was confirmed by Scheibel and Christensen (1965), Stainer (1968) and Relyveld (1969). Stainer further demonstrated the reversion of the toxicity by diluting purified diphtheria toxoid and storing it at 25 C or 34 C ; the toxoid had been prepared by detoxifying crude culture filtrate with formaldehyde alone followed by purification.…”

Section: Notes Reversion Of Toxicity Of Tetanus Toxoidmentioning

confidence: 55%

Reversion of Toxicity of Tetanus Toxoid

Akama

Ito

Yamamoto

et al. 1971

JJMSB

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“…Purification of the toxin before formaldehyde treatment would obviously be preferable, but toxoids obtained in this way show some reversion to toxicity (18). When detoxification of pure toxin was carried out in 0.05 M lysine, the toxoid obtained was stable (7); however, to our knowledge lysine has not been used as yet.…”

Section: Isolationmentioning

confidence: 97%

Isolation and characterization of Corynebacterium diphtheriae nontandem double lysogens hyperproducing CRM197

Rappuoli¹

1983

Appl Environ Microbiol

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Phage 13197'ox, which codes for CRM197, a nontoxic protein immunochemically indistinguishable from diphtheria toxin, was UV induced from a culture of the C7(p197)'x strain. A total of 191 C7(I3197)t'x lysogens were isolated and selected according to the halo produced on TYE agar containing antidiphtheria toxin serum and were further characterized by Southern blots of their chromosomal DNA. Most of the isolates turned out to be monolysogens, but some tandem and nontandem double lysogens were also found. The nontandem double lysogens were stable and capable of giving high yields of CRM197, up to threefold higher than monolysogens. They are, therefore, suitable for large-scale industrial production.

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Irreversible Detoxification of Purified Diphtheria Toxin

Cited by 10 publications

References 5 publications

Effect of formalin toxoiding on Pseudomonas aeruginosa toxin A: biological, chemical, and immunochemical studies

Effect of formalin toxoiding on Pseudomonas aeruginosa toxin A: biological, chemical, and immunochemical studies

Reversion of Toxicity of Tetanus Toxoid

Isolation and characterization of Corynebacterium diphtheriae nontandem double lysogens hyperproducing CRM197

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