title: Characterization of botulinum neurotoxin A subtypes 1 through 5 by investigation of activities in mice, in neuronal cell cultures, and in vitro.
abstract: Botulinum neurotoxins (BoNTs) are synthesized by Clostridium botulinum and exist as seven immunologically distinct serotypes designated A through G. For most serotypes, several subtypes have now been described based on nominal differences in the amino acid sequences. BoNT/A1 is the most well-characterized subtype of the BoNT/A serotype, and many of its properties, including its potency, its prevalence as a food poison, and its utility as a pharmaceutical, have been thoroughly studied. In contrast, much remains unknown of the other BoNT/A subtypes. In this study, BoNT/A subtype 1 (BoNT/A1) to BoNT/A5 were characterized utilizing a mouse bioassay, an in vitro cleavage assay, and several neuronal cell-based assays. The data indicate that BoNT/A1 to -5 have distinct in vitro and in vivo toxicological properties and that, unlike those for BoNT/A1, the neuronal and mouse results for BoNT/A2 to -5 do not correlate with their enzymatic activity. These results indicate that BoNT/A1 to -5 have distinct characteristics, which are of importance for a greater understanding of botulism and for pharmaceutical applications.
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Regina C M
authors.initials: RC
authors.lastname: Whitemarsh
authors.forename: William H
authors.initials: WH
authors.lastname: Tepp
authors.forename: Marite
authors.initials: M
authors.lastname: Bradshaw
authors.forename: Guangyun
authors.initials: G
authors.lastname: Lin
authors.forename: Christina L
authors.initials: CL
authors.lastname: Pier
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Scherf
authors.forename: Eric A
authors.initials: EA
authors.lastname: Johnson
authors.forename: Sabine
authors.initials: S
authors.lastname: Pellett
mesh_terms: D000818:Animals; D001681:Biological Assay; D019274:Botulinum Toxins, Type A / Q000145:classification* / Q000633:toxicity*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
chemical_list: D019274:Botulinum Toxins, Type A
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