Primary Analysis On The Virulence Role Of Quorum Sensing System Of Yersinia Pestis

Backgroud: Yersinia pestis (Y. pestis)is the etiologic agent of bubonic and pneumonic plague, which has claimed millions of lives in human history. The unique pathogenicity is the focus of the recent researches on this pathogen. Quorum sensing is a cell-density dependent global regulation system, which is used for cell to cell communication mediated by the signal molecule, N-acyl-homoserine lactone (AHL). Here, we report the virulence role of quorum sensing system in the pathogenicity of Y. pestis. Methods: By combining the gene mutation technique, HPLC, MS and macrophage apoptosis assays, we isolated and identified the signal molecules of Y. pestis and tested their virulence to macrophage. Using the DNA microarray containing all ORFs of Y. pestis, we compared the transcriptome of the QS mutant to that of its parent strain. With the protein microarray containing the virulence-associated proteins from Y. pestis, the antibody profile of the QS mutant was compared with its parent strain. And then the phenotype differences were analyzed between the QS mutant and its parent. Results: From the supernatant of the wild type strain, two QS signal molecules were identified, C6-HSL and C8-HSL. Both molecules are virulent to macrophage J774A.1. Quorum sensing system controlled the transcription of a large number of genes, including those with basic cellular functions and those encoding proven virulence determinants. The results from antibody profiling showed that many antibodies to the virulence proteins were not detected in the serum from the QS mutant, suggesting that QS influence the expression of these proteins in vivo. The QS mutant is less virulent to cells and mice, as showed by the survival rate in macrophage and LD50 to mice. Conclusion: The quorum sensing system produce two signal molecules, C6-HSL and C8-HSL, which could act as virulence determinants directly. The quorum sensing system controls directly or indirectly a large number of virulence genes, which contribute to the pathogenicity of Y. pestis.