ORGANIZATION AND PHYLOGENETIC INTERRELATIONSHIPS OF GENES ENCODING COMPONENTS OF THE BOTULINUM TOXIN COMPLEX IN PROTEOLYTIC CLOSTRIDIUM-BOTULINUM TYPE-A, TYPE-B, AND TYPE-F - EVIDENCE OF CHIMERIC SEQUENCES IN THE GENE ENCODING THE NONTOXIC NONHEMAGGLUTININ COMPONENT

The cluster of genes encoding components of the botulinum neurotoxin ( BoNT) complex was mapped in proteolytic (group I) Clostridium botulinu m strains encoding BoNT types A, B, acid F. Two different arrangements of genes were found: type A strain 62A and type B strain NCTC 7273 ha ve similar organizations of genes encoding BoNT, the nontoxic nonhemag glutinin component (NTNH), hemagglutinin components, and P-21; type F strain Langeland has genes encoding BoNT, NTNH, and P-21, and a previo usly unidentified open reading frame encoding a protein of 416 amino a cids, A group of type A strains typified by infant strain Kyoto-F, whi ch is unlike type A strain 62A, lacks genes for hemagglutinin componen ts and exhibits an organization similar to that of type F, Sequencing and pairwise analysis revealed the presence of possible chimeric seque nces in some NTNH genes of proteolytic C. botulinum. Discordance in ge nealogical trees derived from different regions of the NTNH genes tvas observed which could be symptomatic of recombination and which may in dicate that the NTNH gene represents a hot spot for such events within the cluster of genes encoding the BoNT complex, It is also evident th at the phylogenetics of the NTNH gene, which is linked to the gene enc oding BoNT, does not mirror the evolutionary history of the BoNT, upon which the C, botulinum species complex is defined and subdivided.