Plague is a vector-borne disease caused by Yersinia pestis. Transmitted by fleas from rodent reservoirs, Y. pestis emerged <6000 years ago from an enteric bacterial ancestor through events of gene gain and genome reduction. It is a highly remarkable model for the understanding of pathogenic bacteria evolution, and a major concern for public health as highlighted by recent human outbreaks. A complex set of virulence determinants, including the Yersinia outer-membrane proteins (Yops), the broad-range protease Pla, pathogen-associated molecular patterns (PAMPs), and iron capture systems play critical roles in the molecular strategies that Y. pestis employs to subvert the human immune system, allowing unrestricted bacterial replication in lymph nodes (bubonic plague) and in lungs (pneumonic plague). Some of these immunogenic proteins as well as the capsular antigen F1 are exploited for diagnostic purposes, which are critical in the context of the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and <48 h for pneumonic plague). Here, we review recent research advances on Y. pestis evolution, virulence factor function, bacterial strategies to subvert mammalian innate immune responses, vaccination, and problems associated with pneumonic plague diagnosis.

Significance: Our past understanding of pathogen evolution has been fragmented because of tendencies to study human clinical isolates. To understand the evolutionary trends of pathogenic bacteria though, we need the context of their nonpathogenic relatives. Our unique and detailed dataset allows description of the parallel evolution of two key human pathogens: the causative agents of plague and Yersinia diarrhea. The analysis reveals an emerging pattern where few virulence-related functions are found in all pathogenic lineages, representing key “foothold” moments that mark the emergence of these pathogens. Functional gene loss and metabolic streamlining are equally complementing the evolution of Yersinia across the pathogenic spectrum.

The aim of this study was to exploit the extensive database on strains of Yersinia collected over more than 50 years in France in order to gain an overview of yersiniosis and potential sources of contamination in this country. The 19 670 strains of Yersinia of human, animal, environmental, and food origin isolated in France were grouped by species, biotype, and serotype. Most human strains (59%) were pathogenic, with a marked predominance of Yersinia enterocolitica bioserotype 4/O:3 (66.8%), followed by Y. enterocolitica 2/O:9 (23.8%) and Yersinia pseudotuberculosis (6.1%). Pigs and pork meat were the nearly exclusive sources of Y. enterocolitica 4/O:3. Other pathogenic strains were rarely isolated from food or environmental samples (0.2%). The major source of pathogenic Yersinia was the animal reservoir, with a remarkable association between Y. enterocolitica 4/O:3 and pigs, Y. pseudotuberculosis and wildlife, Y. enterocolitica 2/O:9 and grazing farm animals, Y. enterocolitica 5/O:2,3 and hares, and Y. enterocolitica 3/O:1,2,3 and chinchillas. The frequency of human infection caused by certain Yersinia subgroups might be related to the frequency of exposure to specific animal sources. In contrast, non-pathogenic Yersinia were commonly isolated from foodstuffs and the environment, most probably accounting for the abundance of non-pathogenic Yersinia recovered from human stools.

The genus Yersinia comprises species that differ widely in their pathogenic potential and public-health significance. Yersinia pestis is responsible for plague, while Yersinia enterocolitica is a prominent enteropathogen. Strains within some species, including Y. enterocolitica, also vary in their pathogenic properties. Phenotypic identification of Yersinia species is time-consuming, labour-intensive and may lead to incorrect identifications. Here, we developed a method to automatically identify and subtype all Yersinia isolates from their genomic sequence. A phylogenetic analysis of Yersinia isolates based on a core subset of 500 shared genes clearly demarcated all existing Yersinia species and uncovered novel, yet undefined Yersinia taxa. An automated taxonomic assignment procedure was developed using species-specific thresholds based on core-genome multilocus sequence typing (cgMLST). The performance of this method was assessed on 1843 isolates prospectively collected by the French National Surveillance System and analysed in parallel using phenotypic reference methods, leading to nearly complete (1814; 98.4 %) agreement at species and infra-specific (biotype and serotype) levels. For 29 isolates, incorrect phenotypic assignments resulted from atypical biochemical characteristics or lack of phenotypic resolution. To provide an identification tool, a database of cgMLST profiles and reference taxonomic information has been made publicly accessible (https://bigsdb.pasteur.fr/yersinia). Genomic sequencing-based identification and subtyping of any Yersinia is a powerful and reliable novel approach to define the pathogenic potential of isolates of this medically important genus.

The genus Yersinia is a large and diverse bacterial genus consisting of human pathogenic species, a fish pathogenic species, and a large number of environmental species. Recently the phylogenetic and population structure of the entire genus was elucidated through genome sequence data of 241 strains encompassing every known species in the genus. Here we report the mining of this enormous data set to create a multi-locus sequence typing-based scheme that can speciate Yersinia strains to a level of resolution equal to whole genome sequencing. Our assay is designed so that it is able to accurately sub-type the important human pathogenic species Y. enterocolitica to whole genome resolution levels. We also report the validation of the scheme on 386 strains from reference laboratory collections across Europe. We propose the scheme to be an important molecular typing system to allow accurate and reproducible speciation of Yersinia isolates, a process often inconsistent in non-specialist laboratories. Additionally our assay is the most phylogenetically informative typing scheme available for Y. enterocolitica.