Yersinia Research Unit, Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris cedex 15, France.
Int J Med Microbiol. 2011 Feb;301(2):105-16. doi: 10.1016/j.ijmm.2010.08.013. Epub 2010 Oct 15.
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.
虽然鼠疫耶尔森菌（Yersinia pestis）和假结核耶尔森菌（Yersinia pseudotuberculosis）在基因上非常相似（大多数染色体基因的核苷酸序列同一性为 97%），但它们表现出非常不同的感染模式。鼠疫耶尔森菌引起的鼠疫通常在没有治疗的情况下是致命的，而假结核耶尔森菌通常会引发非危及生命的肠道症状。这种致病性的巨大差异可能是由于获得了一些物种特异性基因，但也可能是由于它们的转录调控网络存在差异。在这项研究中，我们对在 8 种不同条件下平行生长的鼠疫耶尔森菌和假结核耶尔森菌进行了计算机比较全基因组转录组分析，以确定它们的调控网络是否存在差异。在这项分析中，发现了 304 个在两个物种中都存在的共同基因，它们的转录水平存在显著的种间差异，其中 91%在鼠疫耶尔森菌中表达更高。值得注意的是，在这两个物种中保守的 3 种主要毒力决定因素（pYV 毒力质粒、高致病性岛和 ail 基因座）都在鼠疫耶尔森菌中表达更高。此外，pYV 携带的基因在 37°C 下的诱导在鼠疫耶尔森菌中比在假结核耶尔森菌中要高得多。相反，rovA 转录调节基因在假结核耶尔森菌中转录更多。我们还对鼠疫耶尔森菌和假结核耶尔森菌的转录组数据进行了聚类分析，该分析允许根据它们的表达谱对基因进行分组。该分析确定了一组具有未知功能的基因，根据与已知毒力基因相似的调控模式，这些基因可能是鼠疫耶尔森菌的新潜在毒力决定因素。总之，这是首次对鼠疫耶尔森菌和假结核耶尔森菌的转录谱进行全基因组水平的比较分析。我们的结果表明，鼠疫杆菌更高的致病性不仅可能是由于获得了新的遗传物质，还可能是由于共同关键毒力基因的更高表达水平。因此，这种计算机分析为研究鼠疫耶尔森菌获得致病性和新的潜在毒力因素开辟了新的途径。
