Table_1_The evolutionary diversification of the Salmonella artAB toxin locus.XLSX

Salmonella enterica is a diverse species of bacterial pathogens comprised of >2,500 serovars with variable host ranges and virulence properties. Accumulating evidence indicates that two AB5-type toxins, typhoid toxin and ArtAB toxin, contribute to the more severe virulence properties of the Salmonella strains that encode them. It was recently discovered that there are two distinct types of artAB-like genetic elements in Salmonella: those that encode ArtAB toxins (artAB elements) and those in which the artA gene is degraded and the ArtB homolog, dubbed PltC, serves as an alternative delivery subunit for typhoid toxin (pltC elements). Here, we take a multifaceted approach to explore the evolutionary diversification of artAB-like genetic elements in Salmonella. We identify 7 subtypes of ArtAB toxins and 4 different PltC sequence groups that are distributed throughout the Salmonella genus. Both artAB and pltC are encoded within numerous diverse prophages, indicating a central role for phages in their evolutionary diversification. Genetic and structural analyses revealed features that distinguish pltC elements from artAB and identified evolutionary adaptations that enable PltC to efficiently engage typhoid toxin A subunits. For both pltC and artAB, 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 Salmonella artAB/pltC-like genetic elements and provides a window into the mechanisms of evolution for AB5-type toxins.

沙门氏菌亚科（Salmonella enterica）是一种包含超过2,500个血清型的多样细菌病原体，其宿主范围和致病性特征各异。累积的证据表明，两种AB5型毒素——伤寒毒素（typhoid toxin）和ArtAB毒素，是编码这些毒素的沙门氏菌菌株致病性更强的重要因素。近期研究发现，沙门氏菌中存在两种不同的artAB样基因元件：一种编码ArtAB毒素（artAB元件），另一种则artA基因降解，ArtB的同源基因，被称为PltC，充当伤寒毒素的替代传递亚基（pltC元件）。本研究采用多角度方法，探讨沙门氏菌中artAB样基因元件的进化多样性。我们鉴定出7种ArtAB毒素亚型和4种不同的PltC序列组，它们广泛分布于沙门氏菌属中。artAB和pltC均编码于众多多样的前噬菌体中，表明噬菌体在其进化多样性中扮演了核心角色。遗传学和结构分析揭示了pltC元件与artAB的区别性特征，并确定了PltC能够高效结合伤寒毒素A亚基的进化适应机制。对于pltC和artAB而言，我们发现B亚基的序列尤其多变，尤其是在精细调节其糖基结合口袋化学环境的氨基酸残基方面。本研究为阐明沙门氏菌中artAB/pltC样基因元件的复杂集合提供了框架，并揭示了AB5型毒素进化的机制。