Influence of sensory and regulatory RNAs on the biological fitness and pathogenity of Yersinia pseudotuberculosis

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The enteropathogenic bacterium Y. pseudotuberculosis synthesizes a special set of earlystage virulence genes that promote initial colonization and subsequent penetration of the intestinal tract. These virulence genes are activated by the virulence regulator RovA, which itself is under the control of the post-transcriptional carbon storage regulator system (Csr) implicating small regulatory RNAs. After transcytosis of the intestinal layer, the bacteria switch their genetic program. They repress synthesis of the early virulence factors and induce expression of another set of later-stage virulence factors that are important for the colonization of subepithelial lymphatic tissue and dissemination to deeper tissues. Activation of these genes is only promoted at 37°C and requires the AraC-like regulator LcrF, whose expression is controlled by a FourU-type RNA thermometer. Future work will be directed to elucidate the role and control mechanism by which regulatory RNA are implicated in the coordinate expression of early and late stage virulence genes in response to environmental signals. In this context, we will: (i) identify and characterize components that participate or influence the activity of the Csr-system for early virulence gene expression, (ii) analyze factors that promote the switch to late stage virulence genes expression, and (iii) will analyze the structure, function and regulation of the identified lcrF RNA thermometer with respect to temperature and host cell contact. As regulatory and sensory RNAs seem to play a major role in Yersinia pathogenesis, major efforts will also be directed to identify additional non-coding RNAs that contribute to the coordinate expression of virulence factors. This will gain important new information about the molecular mechanisms how non-coding RNAs orchestrate the expression of virulence genes that are required to initiate and establish an infection.