Effects of purification on the bioavailability of botulinum neurotoxin type A.
Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. They are primarily produced by the gram-positive, anaerobic spore-forming bacterium, Clostridium botulinum. In bacterial cultures, secreted BoNTs are associated with non-toxic accessory proteins forming large complexes. Neurotoxin-associated proteins have been shown to play an important role in the oral toxicity of BoNTs by protecting them from degradation and digestion by gastric acid and enzymes. Most toxicity studies using BoNTs have been performed using highly purified toxin. In this study, the toxicities of purified and crude BoNT/A toxin preparations were compared. Protein components secreted into culture supernatants along with BoNT/A were identified by mass spectrometry and the contribution of extra proteins found in the soluble crude toxin extracts to the toxicity of BoNTs was determined in mouse models of oral and parenteral botulinum intoxication. Analysis of crude toxin composition permitted assessment of the impact of accessory proteins on the oral bioavailability of BoNT/A toxin in food matrices.
Foodborne Contaminants Research Unit, Western Regional Research Center, USDA Agricultural Research Service, Albany, CA 94710, USA. Luisa.Cheng@ARS.USDA.GOV
Luisa W
LW
Cheng
Bruce
B
Onisko
Eric A
EA
Johnson
J Rachel
JR
Reader
Stephen M
SM
Griffey
Ann E
AE
Larson
William H
WH
Tepp
Larry H
LH
Stanker
David L
DL
Brandon
J Mark
JM
Carter
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D018565:Food-Drug Interactions; D007274:Injections, Intraperitoneal; D007441:Intubation, Gastrointestinal; D007928:Lethal Dose 50; D013058:Mass Spectrometry; D051379:Mice
D019274:Botulinum Toxins, Type A