AUTHOR=Ojiakor Adaobi , Gibbs Rachel N. , Chen Zhe , Gao Xiang , Fowler Casey C. 

TITLE=The evolutionary diversification of the Salmonella artAB toxin locus

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1016438

DOI=10.3389/fmicb.2022.1016438

ISSN=1664-302X

ABSTRACT=<p><italic>Salmonella enterica</italic> is a diverse species of bacterial pathogens comprised of &gt;2,500 serovars with variable host ranges and virulence properties. Accumulating evidence indicates that two AB<sub>5</sub>-type toxins, typhoid toxin and ArtAB toxin, contribute to the more severe virulence properties of the <italic>Salmonella</italic> strains that encode them. It was recently discovered that there are two distinct types of <italic>artAB</italic>-like genetic elements in <italic>Salmonella</italic>: those that encode ArtAB toxins (<italic>artAB</italic> elements) and those in which the <italic>artA</italic> gene is degraded and the ArtB homolog, dubbed PltC, serves as an alternative delivery subunit for typhoid toxin (<italic>pltC</italic> elements). Here, we take a multifaceted approach to explore the evolutionary diversification of <italic>artAB</italic>-like genetic elements in <italic>Salmonella</italic>. We identify 7 subtypes of ArtAB toxins and 4 different PltC sequence groups that are distributed throughout the <italic>Salmonella</italic> genus. Both <italic>artAB</italic> and <italic>pltC</italic> are encoded within numerous diverse prophages, indicating a central role for phages in their evolutionary diversification. Genetic and structural analyses revealed features that distinguish <italic>pltC</italic> elements from <italic>artAB</italic> and identified evolutionary adaptations that enable PltC to efficiently engage typhoid toxin A subunits. For both <italic>pltC</italic> and <italic>artAB</italic>, 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 <italic>Salmonella artAB</italic>/<italic>pltC</italic>-like genetic elements and provides a window into the mechanisms of evolution for AB<sub>5</sub>-type toxins.</p>