In silico comparison of Yersinia pestis and Yersinia pseudotuberculosis transcriptomes reveals a higher expression level of crucial virulence determinants in the plague bacillus

Abstract

Although Yersinia pestis and Yersinia pseudotuberculosis are genetically very similar (97% nucleotide sequence identity for most of the chromosomal genes), they exhibit very different patterns of infection. Y. pestis causes plague which is usually fatal in the absence of treatment, whereas Y. pseudotuberculosis generally triggers non-life-threatening intestinal symptoms. This drastic difference in pathogenicity may result from the acquisition of a few species-specific genes, but also from differences in their transcriptional regulation networks. In this study, we performed an in silico comparative whole-genome transcriptome analysis of Y. pestis and Y. pseudotuberculosis grown in parallel under 8 distinct conditions to determine whether they exhibit differences in their regulatory networks. In this analysis, 304 genes common to both species were found to display significant inter-species differences in transcriptional levels, with 91% of them being more expressed in Y. pestis. Remarkably, 3 major virulence determinants conserved in the 2 species (the pYV virulence plasmid, the High Pathogenicity Island, and the ail locus) were among the genes more expressed in Y. pestis. Furthermore, the induction at 37 °C of pYV-borne genes was considerably greater in Y. pestis than in Y. pseudotuberculosis. Conversely, the rovA transcriptional regulator gene was more transcribed in Y. pseudotuberculosis. We also performed a clustering analysis of the transcriptome data of both Y. pestis and Y. pseudotuberculosis, which allowed to group genes according to their expression profiles. This analysis identified groups of genes with unknown functions which, based on regulation patterns similar to those of known virulence genes, are potential new virulence determinants in Y. pestis. In conclusion, this is the first comparative analysis at the whole-genome level of the transcription profiles of Y. pestis and Y. pseudotuberculosis. Our results suggest that the higher pathogenicity of the plague bacillus may not only result from the acquisition of new genetic material, but also from a higher expression level of common crucial virulence genes. This in silico analysis thus opens new avenues for investigating Y. pestis gain of pathogenicity and new potential virulence factors.