Genetic characteristics of toxigenic Clostridia and toxin gene evolution

Clostridia comprise a heterogenous group of environmental bacteria containing 15 pathogenic species, which produce the most potent toxins. The origin of toxins is still enigmatic. It is hypothesized that toxins exhibiting an enzymatic activity have derived from hydrolytic enzymes, which are abundantly secreted by these bacteria, and that pore-forming toxins have evolved from an ancestor transmembrane protein. The presence of related toxin genes in distinct Clostridium species and the variability of some toxin genes support horizontal toxin gene transfer and subsequent independent evolution from strain to strain. Clostridium perfringens toxin genes involved in myonecrosis, mainly alpha toxin and perfringolysin genes, are chromosomally located, whereas toxin genes responsible for intestinal and food borne diseases are localized on plasmids except the enterotoxin gene which can be located either on the chromosome or plasmids. The distribution of these plasmids containing one or several toxin genes accounts for the diverse C. perfringens toxinotypes. Clostridium difficile strains show a high genetic variability. But in contrast to C. perfringens, toxin genes are clustered in pathogenicity locus located on chromosome. The presence of related toxin genes in distinct clostridial species like Clostridium sordellii, Clostridium novyi, and C. perfringens supports interspecies mobilization of this locus. The multiple C. difficile toxinotypes based on toxin gene variants possibly reflect strain adaptation to the intestinal environment. Botulinum toxin genes also show a high level of genetic variation. They have a diverse genetic localization including chromosome, plasmid or phage, and are spread in various Clostridium species (Clostridium botulinum groups, Clostridium argentinense, Clostridium butyricum, Clostridium baratii). Exchange of toxin genes not only include transfers between Clostridium species but also between Clostridium and other bacterial species as well as eukaryotic cells as supported by the wide distribution of related pore-forming toxins of the aerolysin family in various clostridial and non-clostridial species, animal, mushroom and plant.