Pathogenicity of botulinum C·D mosaic toxins in animals

Abstract

Clostridium botulinum types C and D are related to avian and mammalian botulism. Immunological cross-reactions between the two neurotoxins (BoNTs/C and D) remain to be elucidated. In avian botulism, we found that the isolates in Japan produced a toxin that was neutralized by both type C and D antitoxins. Analyses of the nucleotide sequences of several strains demonstrated that the BoNT gene comprises two-thirds of BoNT/C and one-third of the BoNT/D gene, suggesting that the avian isolates produce the mosaic of BoNT/C and BoNT/D. The isolate harboring C/D mosaic toxin gene may be characteristic of subtype C α , which was considered to produce C1 and D toxic factors. In type D, some strains (such as strain South African) produced a D/C mosaic toxin. In Japan, bovine botulism has occurred sporadically since 1999. We genetically and immunologically examined the BoNT of bovine botulism-related isolates. Eventually all bovine isolates produced the D/C mosaic neurotoxin, showing that it exhibits the highest lethal activity in mice compared with those of other types of BoNTs. We prepared four sets of primers to differentiate the genes for the mosaic and authentic forms. PCR with the primer sets was useful for typing mosaic toxins. These results indicate that the C·D mosaic neurotoxins are probably a pathogenic agent causing certain forms of avian and bovine botulism.