Botulinum neurotoxin subtype A2 enters neuronal cells faster than subtype A1.
Botulinum neurotoxins (BoNTs), the causative agent of human botulism, are the most potent naturally occurring toxins known. BoNT/A1, the most studied BoNT, is also used as an important biopharmaceutical. In this study, the biological activity of BoNT/A1 is compared to that of BoNT/A2 using neuronal cell models. The data obtained indicate faster and increased intoxication of neuronal cells by BoNT/A2 than BoNT/A1, and that the mechanism underlying this increased toxicity is faster and more efficient cell entry that is independent of ganglioside binding. These results have important implications for the development of new BoNT based therapeutics and BoNT countermeasures.
Department of Bacteriology, University of Wisconsin, Madison, Madison, WI 53706, USA.
Christina L
CL
Pier
Chen
C
Chen
William H
WH
Tepp
Guangyun
G
Lin
Kim D
KD
Janda
Joseph T
JT
Barbieri
Sabine
S
Pellett
Eric A
EA
Johnson
D000818:Animals; D015153:Blotting, Western; D019274:Botulinum Toxins, Type A / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D013116:Spinal Cord / Q000166:cytology; D016708:Synaptophysin / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D013997:Time Factors; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D005732:Gangliosides; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D019274:Botulinum Toxins, Type A; D020696:rab5 GTP-Binding Proteins