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

Abstract

While advances in genomic sequencing have highlighted significant strain variability between and within Salmonella 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 Salmonella adhesin/invasin PagN influences bacterial interaction with their receptors. The Salmonella enterica, subspecies enterica serovar Typhi (S. 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 Salmonella enterica, subspecies enterica serovar Typhimurium (S. 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 S. Typhi PagN. PagN sequence comparisons from 542 Salmonella strains for six representative S. enterica serovars and S. diarizonae 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 Salmonella stains, subspecies and serovars.

The Invasin and Complement-Resistance Protein Rck of Salmonella is More Widely Distributed than Previously Expected

“…Several reports demonstrated that even minor variation in the amino acid sequence might generate important variation in protein function ( 33 , 34 ). We therefore sought to evaluate the impact of the protein polymorphism observed in Rck sequences on its ability to both promote bacterial invasion of host cells and to protect these bacteria from complement attack.…”

“…Notably, several studies designed by the Schifferli lab have highlighted a host-specific tropism of strains according to FimH adhesin allelic variants ( 34 , 43 ). More recently, they characterized the functionality and the affinity of several allelic variants of the PagN invasin of Salmonella with its interactants and highlighted the importance of two amino acids in PagN binding to laminin and mammalian cells as well as in cell invasion ( 33 ). Here, the functionality of 14 variants of Rck, engineered in our laboratory to reproduce the proteins presenting polymorphisms in the different domains of the protein (i.e., signal peptide, all four extracellular loops, transmembrane β-barrel regions), was assessed.…”

Listeria monocytogenes Invasion Into Sheep Kidney Epithelial Cells Depends on InlB, and Invasion Efficiency Is Modulated by Phylogenetically Defined InlB Isoforms

“…Allelic variation of the Salmonella virulence factor PagN, which participates in the colonization of enterocytes, affects the invasive properties of different Salmonella subspecies and serovars, thereby binding Salmonella typhi to human enterocytes better than Salmonella typhimurium does ( Wu et al, 2020 ). The Yersinia pseudotuberculosis gene encoding the Rho-modifying YopE toxin differs by three SNPs in highly virulent human FESLF strains from low-virulence strains, but all three SNPs are nonsynonymous, thus suggesting their positive selection and role in strain virulence ( Timchenko et al, 2016 ).…”

Investigation of the invasion mechanism mediated by the outer membrane protein PagN of Salmonella Typhimurium

“…enterica , and also within other subspecies and species but to a lower extent. This high conservation does not, however, predict the functionality of the protein as it has recently been shown that only one substitution in loop 1 or 2 could be sufficient to increase the adhesive and invasive properties of PagN [ 35 ]. Further studies are required to decipher the amino acids/peptides important for PagN function, especially those in the predicted outer membrane loops.…”