Unique biological activity of botulinum D/C mosaic neurotoxin in murine species

Keiji Nakamura, Tomoko Kohda, Yuto Shibata, Kentaro Tsukamoto, Hideyuki Arimitsu, Mitsunori Hayashi, Masafumi Mukamoto, Nobuyuki Sasakawa, Shunji Kozaki

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Abstract

Clostridium botulinum types C and D cause animal botulism by the production of serotype-specific or mosaic botulinum neurotoxin (BoNT). The D/C mosaic BoNT (BoNT/DC), which is produced by the isolate from bovine botulism in Japan, exhibits the highest toxicity to mice among all BoNTs. In contrast, rats appeared to be very resistant to BoNT/DC in type C and D BoNTs and their mosaic BoNTs. We attempted to characterize the enzymatic and receptor-binding activities of BoNT/DC by comparison with those of type C and D BoNTs (BoNT/C and BoNT/D). BoNT/DC and D showed similar toxic effects on cerebellar granule cells (CGCs) derived from the mouse, but the former showed less toxicity to rat CGCs. In recombinant murine-derived vesicleassociated membrane protein (VAMP), the enzymatic activities of both BoNTs to rat isoform 1 VAMP (VAMP1) were lower than those to the other VAMP homologues. We then examined the physiological significance of gangliosides as the binding components for types C and D, and mosaic BoNTs. BoNT/DC and C were found to cleave an intracellular substrate of PC12 cells upon the exogenous addition of GM1a and GT1b gangliosides, respectively, suggesting that each BoNT recognizes a different ganglioside moiety. The effect of BoNT/DC on glutamate release from CGCs was prevented by cholera toxin B-subunit (CTB) but not by a site-directed mutant of CTB that did not bind to GM1a. Bovine adrenal chromaffin cells appeared to be more sensitive to BoNT/DC than to BoNT/C and D. These results suggest that a unique mechanism of receptor binding of BoNT/DC may differentially regulate its biological activities in animals.

Original languageEnglish
Pages (from-to)2886-2893
Number of pages8
JournalInfection and Immunity
Volume80
Issue number8
DOIs
Publication statusPublished - 01-08-2012

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Dilatation and Curettage
Neurotoxins
Botulism
Membrane Proteins
Gangliosides
Cholera Toxin
Vesicle-Associated Membrane Protein 1
Clostridium botulinum type D
Clostridium botulinum type C
Chromaffin Cells
Poisons
PC12 Cells
Glutamic Acid
Japan
Protein Isoforms

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Nakamura, K., Kohda, T., Shibata, Y., Tsukamoto, K., Arimitsu, H., Hayashi, M., ... Kozaki, S. (2012). Unique biological activity of botulinum D/C mosaic neurotoxin in murine species. Infection and Immunity, 80(8), 2886-2893. https://doi.org/10.1128/IAI.00302-12
Nakamura, Keiji ; Kohda, Tomoko ; Shibata, Yuto ; Tsukamoto, Kentaro ; Arimitsu, Hideyuki ; Hayashi, Mitsunori ; Mukamoto, Masafumi ; Sasakawa, Nobuyuki ; Kozaki, Shunji. / Unique biological activity of botulinum D/C mosaic neurotoxin in murine species. In: Infection and Immunity. 2012 ; Vol. 80, No. 8. pp. 2886-2893.
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Nakamura, K, Kohda, T, Shibata, Y, Tsukamoto, K, Arimitsu, H, Hayashi, M, Mukamoto, M, Sasakawa, N & Kozaki, S 2012, 'Unique biological activity of botulinum D/C mosaic neurotoxin in murine species', Infection and Immunity, vol. 80, no. 8, pp. 2886-2893. https://doi.org/10.1128/IAI.00302-12

Unique biological activity of botulinum D/C mosaic neurotoxin in murine species. / Nakamura, Keiji; Kohda, Tomoko; Shibata, Yuto; Tsukamoto, Kentaro; Arimitsu, Hideyuki; Hayashi, Mitsunori; Mukamoto, Masafumi; Sasakawa, Nobuyuki; Kozaki, Shunji.

In: Infection and Immunity, Vol. 80, No. 8, 01.08.2012, p. 2886-2893.

Research output: Contribution to journalArticle

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AU - Kohda, Tomoko

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AU - Tsukamoto, Kentaro

AU - Arimitsu, Hideyuki

AU - Hayashi, Mitsunori

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