The evolutionary diversification of the toxin locus.

is a diverse species of bacterial pathogens comprised of >2,500 serovars with variable host ranges and virulence properties. Accumulating evidence indicates that two AB-type toxins, typhoid toxin and ArtAB toxin, contribute to the more severe virulence properties of the strains that encode them. It was recently discovered that there are two distinct types of -like genetic elements in : those that encode ArtAB toxins ( elements) and those in which the gene is degraded and the ArtB homolog, dubbed PltC, serves as an alternative delivery subunit for typhoid toxin ( elements). Here, we take a multifaceted approach to explore the evolutionary diversification of -like genetic elements in . We identify 7 subtypes of ArtAB toxins and 4 different PltC sequence groups that are distributed throughout the genus. Both and are encoded within numerous diverse prophages, indicating a central role for phages in their evolutionary diversification. Genetic and structural analyses revealed features that distinguish elements from and identified evolutionary adaptations that enable PltC to efficiently engage typhoid toxin A subunits. For both and , we find that the sequences of the B subunits are especially variable, particularly amongst amino acid residues that fine tune the chemical environment of their glycan binding pockets. This study provides a framework to delineate the remarkably complex collection of /-like genetic elements and provides a window into the mechanisms of evolution for AB-type toxins.