Supertoxic complexes of botulinum toxins

• Published in: Žurnal mikrobiologii, ėpidemiologii i immunobiologii no. 5; p. 40
• Main Author: Vertiev, Iu V
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01-09-1999
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - toxicity; Botulinum Toxins - analysis; Botulinum Toxins - chemistry; Botulinum Toxins - genetics; Botulinum Toxins - toxicity; Clostridium botulinum - genetics; Clostridium botulinum - pathogenicity; Dose-Response Relationship, Drug; Lethal Dose 50; Mice; Structure-Activity Relationship
• ISSN: 0372-9311

The super-toxic super-complexes (SSC) of botulinic neurotoxins, types A and B, have been isolated. The preparation of type A SSC (SSC/A) consist of the proteolyzed form of type A botulinic neurotoxin (BoNT/A), 50 and 90 kD, nontoxic nonhemagglutinating protein of 140 kD (NTNH140) in the nonproteolyzed form, hemagglutinin of 17 kD (Ha17), hemagglutinin of 34 kD (Ha34) and the proteolyzed form of hemagglutinin of 70 kD (Ha70) (20 and 50 kD). The preparations of type B SSC (SSC/B) consist of the nonproteolyzed form of type B botulinic neurotoxin (BoNT/B) of 150 kD, the proteolyzed form of BoNT/B of 150 kD (45 and 105 kD), the nonproteolyzed form of NTNH140, Ha17, Ha34 and two nonidentified proteins (32 and 40 kD). As shown in this study, toxic complexes both in native toxins and in the preparations of SSC do not dissociate for several weeks at pH 8.0 and for 18 hours in 3% SDS, as well as after treatment with RNAase or 1 M NaCl. Some part of SSC/A (neurotoxin and Ha70) has been found to dissociate in 3% SDS after 1-hour incubation at 22 degrees C after the addition of 2-ME. The preparations of SSC contain nucleic acids (A260 nm/A280 nm = 2.0), supposedly ensuring the stability of the complexes. In contrast to the L-forms of Clostridium botulinum toxins, the preparations of SSC/A and SSC/B have been found to possess increased toxicity. The specific toxicity of SSC/A has proved to be 1-2 x 10(9) DLM per 1 OD280 nm and that of SSC/B, from 5 x 10(8) to 1 x 10(9) DLM per OD280 nm. One minimal lethal oral dose of these SSC preparations for mice was less than 10 DLM, introduces intraperitoneally.