1887

Abstract

types C and D produce a 16 S (500 kDa) toxin that is formed by conjugation of neurotoxin with a non-toxic component (nonTox). The amino acid sequences of type C and D nonTox components are almost identical. In a previous report it was proposed that nonTox is necessary for the effective absorption of the toxin from the small intestine. This suggested the hypothesis that mucosal immunity against nonTox in the small intestine might prevent the absorption of both C- and D-16 S toxins. The nonTox was purified from a mutant strain, (C)-N71, that does not produce neurotoxin. This nonTox or detoxified C-16 S toxin were mixed with adjuvant (a mutant form of heat-labile toxin of ), and inoculated into mice the nasal or oral route, or both. The mice inoculated nasally four times with nonTox or toxoid produced high levels of antibodies (including IgA) against the immunogens, both in intestinal fluids and sera. When these nonTox-immunised mice were challenged orally with 2 and 20 oral minimum lethal doses (MLD) of C- or D-16 S toxins, the same results were obtained with both C and D; the mice survived after challenge with 2 MLD of either C or D but were killed by 20 MLD of either toxin although the time to death was significantly longer than in the control non-immunised mice. These results indicate that the local anti-nonTox antibodies reduce absorption of both C- and D-16 S toxins from the small intestine. The C-16 S toxoid-immunised mice showed similar behaviour with type D toxin challenge, probably due to the same mechanism, but were protected against 20 MLD of C-16 S toxin.

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2002-10-01
2019-11-13
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References

  1. Ohyama T, Watanabe T, Fujinaga Y.et al. Characterization of nontoxic-nonhemagglutinin component of the two types of progenitor toxin (M and L) produced by Clostridium botulinum Type D CB-16. Microbiol Immunol 1995;; 39: 457–465.[CrossRef]
    [Google Scholar]
  2. Fujinaga Y, Inoue K, Shimazaki S.et al. Molecular construction of Clostridium botulinum type C progenitor toxin and its gene organization. Biochem Biophys Res Commun 1994;; 205: 1291–1298.[CrossRef]
    [Google Scholar]
  3. Fujita R, Fujinaga Y, Inoue K, Nakajima H, Kumon H, Oguma K. Molecular characterization of two forms of nontoxic-nonhemagglutinin components of Clostridium botulinum type A progenitor toxins. FEBS Lett 1995;; 376: 41–44.[CrossRef]
    [Google Scholar]
  4. Inoue K, Fujinaga Y, Watanabe T.et al. Molecular composition of Clostridium botulinum type A progenitor toxins. Infect Immun 1996;; 64: 1589–1594.
    [Google Scholar]
  5. Inoue K, Fujinaga Y, Honke K.et al. Characterization of haemagglutinin activity of Clostridium botulinum type C and D 16 S toxins, and one subcomponent of haemagglutinin (HA 1). Microbiology 1999;; 145: 2533–2542.
    [Google Scholar]
  6. Oguma K, Syuto B, Iida H, Kubo S. Antigenic similarity of toxins produced by Clostridium botulinum type C and D strains. Infect Immun 1980;; 30: 656–660.
    [Google Scholar]
  7. Oguma K, Fujinaga Y, Inoue K. Clostridium botulinum toxin. J Toxicol Toxin Rev 1997;; 16: 253–266.[CrossRef]
    [Google Scholar]
  8. Minton NP. Molecular genetics of clostridial neurotoxins. Curr Top Microbiol Immunol 1995;; 195: 161–194.
    [Google Scholar]
  9. Ohishi I, Sugii S, Sakaguchi G. Oral toxicities of Clostridium botulinum toxins in response to molecular size. Infect Immun 1977;; 16: 107–109.
    [Google Scholar]
  10. Ohishi I, Sakaguchi G. Oral toxicities of Clostridium botulinum type C and D toxins of different molecular sizes. Infect Immun 1980;; 28: 303–309.
    [Google Scholar]
  11. Sugii S, Ohishi I, Sakaguchi G. Intestinal absorption of botulinum toxins of different molecular sizes in rats. Infect Immun 1977;; 17: 491–496.
    [Google Scholar]
  12. Maksymowych AB, Reinhard M, Malizio CJ, Goodnough MC, Johnson EA, Simpson LL. Pure botulinum neurotoxin is absorbed from the stomach and small intestine and produces peripheral neuromuscular blockade. Infect Immun 1999;; 67: 4708–4712.
    [Google Scholar]
  13. Fujinaga Y, Inoue K, Watanabe S.et al. The haemagglutinin of Clostridium botulinum type C progenitor toxin plays an essential role in binding of toxin to the epithelial cells of guinea pig small intestine leading to the efficient absorption of the toxin. Microbiology 1997;; 143: 3841–3847.[CrossRef]
    [Google Scholar]
  14. Fujinaga Y, Inoue K, Nomura T.et al. Identification and characterization of functional subunits of Clostridium botulinum type A progenitor toxin involved in binding to intestinal microvilli and erythrocytes. FEBS Lett 2000;; 467: 179–183.[CrossRef]
    [Google Scholar]
  15. Inoue K, Fujinaga Y, Honke K.et al. Clostridium botulinum type A haemagglutinin positive progenitor toxin (HA+-PTX) binds to oligosaccharides containing Galβ 1-4GlcNAc through one subcomponent of haemagglutinin (HA1). Microbiology 2001;; 147: 811–819.
    [Google Scholar]
  16. Mahmut N, Inoue K, Fujinaga Y.et al. Characterization of monoclonal antibodies against haemagglutinin associated with Clostridium botulinum type C neurotoxin. J Med Microbiol 2002;; 51: 286–294.
    [Google Scholar]
  17. Oguma K, Iida H, Inoue K. Observations on nonconverting phage, c-n71, obtained from a nontoxigenic strain of Clostridium botulinum type C. Jpn J Microbiol 1975;; 19: 167–172.[CrossRef]
    [Google Scholar]
  18. Oguma K, Iida H, Shiozaki M. Phage conversion to hemagglutinin production in Clostridium botulinum types C and D. Infect Immun 1976;; 14: 597–602.
    [Google Scholar]
  19. Hauser D, Gibert M, Eklund MW, Boquet P, Popoff MR. Comparative analysis of C3 and botulinum neurotoxin genes and their environment in Clostridium botulinum types C and D. J Bacteriol 1993;; 175: 7260–7268.
    [Google Scholar]
  20. Tsuji T, Yokochi T, Kamiya H, Kawamoto Y, Miyama A, Asano Y. Relationship between a low toxicity of the mutant A subunit of enterotoxigenic Escherichia coli enterotoxin and its strong adjuvant action. Immunology 1997;; 90: 176–182.[CrossRef]
    [Google Scholar]
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