The Not so Good, the Bad and the Ugly: Differential Bacterial Adhesion and Invasion Mediated by PagN Allelic Variants.

While advances in genomic sequencing have highlighted significant strain variability between and within serovars, only a few protein variants have been directly related to evolutionary adaptation for survival, such as host specificity or differential virulence. The current study investigated whether allelic variation of the adhesin/invasin PagN influences bacterial interaction with their receptors. The serovar Typhi ( Typhi) allelic variant of PagN was found to bind significantly better to different enterocytes as well as to the extracellular matrix protein laminin than did the major serovar Typhimurium ( Typhimurium) allele. The two alleles differed at amino acid residues 49 and 109 in two of the four predicted PagN surface loops, and residue substitution analysis revealed that a glutamic acid at residue 49 increased the adhesive and invasive properties of Typhi PagN. PagN sequence comparisons from 542 strains for six representative serovars and further supported the role of glutamic acid at residues 49 and 109 in optimizing adhesion to cells and laminin, as well as for cell invasion. In summary, this study characterized unique residues in allelic variants of a virulence factor that participates in the colonization and invasive properties of different stains, subspecies and serovars.