Project description:Following a pacemaker implantation, a 75-years-old patient suffered from five successive bacteremia episodes between in 1999 and 2013, during which five bacterial strains were isolated. Phenotypic and whole-genome sequencing analysis of four isolates identified the strains as Yersinia enterocolitica bioserotype 4/O:3. Phylogenetic reconstruction showed that the patient was chronically infected by the same strain, which evolved within the host during 14 years. Single-nucleotide polymorphhism (SNP) analysis indicates that the last two isolates which displayed severe growth defects in vitro and acquired resistance to quinolones, evolved in parallel and formed two independent lineages within the host. Pan-genome analysis and genome comparison showed that their common evolution was characterized by 41 small insertion/deletion events and loss of three large DNA fragments. These mutations, which may account for the observed growth defect and also for the appearance of vegetations on the pacemaker, support antibiotics tolerance. Quinolone resistance was acquired through a so far undescribed deletion in the gyrA gene. 140 genes containing mutations vertically acquired from a common ancestor were also identified in the two lineages. A phylogenetic analysis by maximum likelihood identified two genes presenting a positive selection signal, suggesting that these mutations provided a survival advantage to bacteria during chronic infection. This is the first report allowing identification of genetic changes associated to within-host adaptation of a pathogenic Yersinia species.
Project description:BackgroundYersinia enterocolitica strains responsible for mild gastroenteritis in humans are very diverse with respect to their metabolic and virulence properties. Strain W22703 (biotype 2, serotype O:9) was recently identified to possess nematocidal and insecticidal activity. To better understand the relationship between pathogenicity towards insects and humans, we compared the W22703 genome with that of the highly pathogenic strain 8081 (biotype1B; serotype O:8), the only Y. enterocolitica strain sequenced so far.ResultsWe used whole-genome shotgun data to assemble, annotate and analyse the sequence of strain W22703. Numerous factors assumed to contribute to enteric survival and pathogenesis, among them osmoregulated periplasmic glucan, hydrogenases, cobalamin-dependent pathways, iron uptake systems and the Yersinia genome island 1 (YGI-1) involved in tight adherence were identified to be common to the 8081 and W22703 genomes. However, sets of ~550 genes revealed to be specific for each of them in comparison to the other strain. The plasticity zone (PZ) of 142 kb in the W22703 genome carries an ancient flagellar cluster Flg-2 of ~40 kb, but it lacks the pathogenicity island YAPI(Ye), the secretion system ysa and yts1, and other virulence determinants of the 8081 PZ. Its composition underlines the prominent variability of this genome region and demonstrates its contribution to the higher pathogenicity of biotype 1B strains with respect to W22703. A novel type three secretion system of mosaic structure was found in the genome of W22703 that is absent in the sequenced strains of the human pathogenic Yersinia species, but conserved in the genomes of the apathogenic species. We identified several regions of differences in W22703 that mainly code for transporters, regulators, metabolic pathways, and defence factors.ConclusionThe W22703 sequence analysis revealed a genome composition distinct from other pathogenic Yersinia enterocolitica strains, thus contributing novel data to the Y. enterocolitica pan-genome. This study also sheds further light on the strategies of this pathogen to cope with its environments.
