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.genomics metabolic streamlining | pathoadaptation | Enterobacteriaceae B acterial species are defined on the basis of phenotypic characteristics, such as cellular morphology and biochemical characteristics, as well as DNA-DNA hybridization and 16S rRNA comparison. Using high-throughput whole-genome approaches we can now move beyond classic methods and develop population frameworks to reconstruct accurate inter-and intraspecies relationships and gain insights into the complex patterns of gene flux that define different taxonomic groups.Bacterial whole-genome sequencing has revealed enormous heterogeneity in gene content, even between members of the same species. From a bacterial perspective the acquisition of new genes provides the flexibility to adapt and exploit novel niches and opportunities. From a human perspective, integration of genes by bacteria has been directly linked to the emergence of new pathogenic clones, often from formerly harmless lineages (1, 2). In addition to gene gain, gene loss is also strongly associated with host restriction in acutely pathogenic bacterial species, such as Yersinia pestis and Salmonella enterica serovars, including Salmonella Typhi (3-5), where gene loss can remove functions unnecessary in the new niche (6). These specialist pathogens show a much higher frequency of functional gene loss than closely related host generalist pathogens, such as Yersinia pseudotuberculosis (7).Previous Yersinia genome studies (8, 9) have examined the evolution of pathogenicity by comparing strains from a selection of species or species subtypes within the genus, limiting our understanding of the evolutionary context of individual species. The majority of the Yersinia species are found in the environment and do not cause disease in mammals. Three species are known as human pathogens: the plague bacillus Y. pestis and the enteropathogens Yersinia enterocolitica and Y. pseudotuberculosis. SignificanceOur past understanding of pathogen evo...

Use of Whole-Genus Genome Sequence Data To Develop a Multilocus Sequence Typing Tool That Accurately Identifies Yersinia Isolates to the Species and Subspecies Levels

“…Recent work by our group definitively characterized the phy-logeny of the entire Yersinia genus using genome sequences of 241 strains encompassing the full diversity within the genus (13). Particular attention was given to Y. enterocolitica, of which 94 strains encompassing all biotypes and serotypes were sequenced.…”

“…Particular attention was given to Y. enterocolitica, of which 94 strains encompassing all biotypes and serotypes were sequenced. The whole-genus phylogeny was constructed using 84 housekeeping genes that are located on 23 syntenic blocks, regions of DNAcontaining genes conserved across the genus, and showed the presence of 14 species clusters as determined by Bayesian analysis of population structure (BAPS) software (13). The resulting phylogeny also accurately distinguished Y. pestis as a distinct clone of Y. pseudotuberculosis and phylogenetically split Y. enterocolitica on the basis of high-pathogenic, low-pathogenic, and nonpathogenic biotypes (13).…”

The genetic analysis of Enterobacteriaceae plasmids to provide insights into the acquisition and spread of the blaNDM gene

“…Isolates included in this study involve various species of the Enterobacteriaceae collected for eight different studies (268)(269)(270)(271)(272)(273)(274). Each study lies within a 'global' or 'geographical/region specific' scope according to the list of countries covered by their strain collection (Appendix C; Table S3).…”

“…Contigs from each isolate were obtained as previously described (268)(269)(270)(271)(272)(273)(274). A collective total of 1683 isolates passed QC based on total alignment length and number of contigs.…”

“…Here, we perform an investigation of 1683 isolates of different species within the Enterobacteriaceae using an opportunistic and non-selective approach of existing sequencing data from several global and regional studies (268)(269)(270)(271)(272)(273)(274). Three studies were designed to capture the global diversity of Klebsiella pneumoniae (271), the Yersinia genus (273), and Enterotoxigenic E. coli (ETEC) (274) were included, as well as five regional studies looking …”