Parallel independent evolution of pathogenicity within the genus Yersinia

Abstract

The genus Yersinia has been used as a model system to study pathogen evolution. Using whole-genome sequencing of all Yersinia species, we delineate the gene complement of the whole genus and define patterns of virulence evolution. Multiple distinct ecological specializations appear to have split pathogenic strains from environmental, nonpathogenic lineages. This split demonstrates that contrary to hypotheses that all pathogenic Yersinia species share a recent common pathogenic ancestor, they have evolved independently but followed parallel evolutionary paths in acquiring the same virulence determinants as well as becoming progressively more limited metabolically. Shared virulence determinants are limited to the virulence plasmid pYV and the attachment invasion locus ail. These acquisitions, together with genomic variations in metabolic pathways, have resulted in the parallel emergence of related pathogens displaying an increasingly specialized lifestyle with a spectrum of virulence potential, an emerging theme in the evolution of other important human pathogens.

Keywords: Enterobacteriaceae; genomics metabolic streamlining; pathoadaptation.

Fig. 1.

The phylogeny of the genus Yersinia and the virulence plasmid pYV. Maximum-likelihood phylogenetic tree of the genus Yersinia based on the concatenated sequence of 84 housekeeping genes. Current species assignments based on biochemical typing (36) (color circle borders) are contrasted with the species complexes (colored circles) as allocated by BAPS. The SC for the Y. frederiksenii type strain (8) is depicted by an asterisk. Arrows show the independent acquisition events of the virulence plasmid pYV. The pYV plasmid tree for pathogenic Y. enterocolitica and Y. pseudotuberculosis samples is shown.

Fig. 2.

Distribution of pathogenicity determinants across the genus. Three broad groups of pathogenicity determinants present in the genus are highlighted (see text and Dataset S1). Heatmap colors are based upon average amino acid identity either of single genes or as an average of the amino acid identity across the genes in the operon, as indicated. The percent identities were identified using BLAST searches of the assembled genomes. The corresponding species complexes (Fig. 1) and PGs (Fig. 3) are highlighted. Comparator sequences used: 1, Y. enterocolitica (YE8081); 2, Y. enterocolitica (YE212/02); 3, Y. pseudotuberculosis (IP32953); 4, Y. pestis (CO92); 5, Y. intermedia (ATCC29909). Gene names are given for pathogencity determinants, operons are labeled with their names. Abbreviations: Flg, flagella cluster; Ygt, Yersinia genus T3SS; 2-CS, two component system; eff, effectors; reg, regulator; app, apparatus; mem, membrane proteins; met (salv), methionine (salvage); YAPI, Yersinia adhesion pathogenicity island; T2SS, type 2 secretion system (general secretion pathway); fes/fep, siderophore operon; tcPAI, toxin complex pathogenicity island; HPI, high-pathogenicity island.

Fig. 3.

The phylogeny of Y. enterocolitica. Maximum-likelihood phylogeny for the species based on SNPs across the whole genome excluding laterally acquired elements and phages. Lineages are characterized by biotype, biological origin, country of origin, and serotype. The biochemical tests used for biotyping (36) of Y. enterocolitica are presented for each strain. Shaded boxes highlight results of genomic serotype analysis differing from in vitro results. Biotyping reactions are: 1, salicin acid production; 2, pyrazinamidase activity; 3, esculin hydrolysis; 4, lipase activity; 5, indole production; 6, xylose acid production; 7, trehalose acid production; 8, sorbose acid production; 9, nitrate reduction; 10, ornithine decarboxylase; 11, Voges-Proskauer test; 12, inositol acid production.