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

肠道致病菌Y.假结核病合成一组特殊的早期毒力基因，其促进初始定殖和随后的肠道渗透。这些毒力基因由毒力调节因子RovA激活，RovA本身受涉及小调控RNA的转录后碳储存调节因子系统（Csr）的控制。在转胞吞肠层后，细菌转换其遗传程序。它们抑制早期毒力因子的合成并诱导另一组晚期毒力因子的表达，所述晚期毒力因子对于上皮下淋巴组织的定殖和向更深组织的传播是重要的。这些基因的激活仅在37 ° C下促进，并且需要AraC样调节因子LcrF，其表达由FourU型RNA温度计控制。未来的工作将致力于阐明调控RNA在早期和晚期毒力基因响应环境信号的协调表达中的作用和控制机制。在这方面，我们将：（i）鉴定和表征参与或影响Csr系统早期毒力基因表达活性的组分，（ii）分析促进向晚期毒力基因表达转换的因素，以及（iii）分析鉴定的lcrF RNA温度计相对于温度和宿主细胞接触的结构、功能和调节。由于调控和感觉RNA似乎在耶尔森氏菌的发病机制中起主要作用，因此还将努力鉴定有助于毒力因子协调表达的其他非编码RNA。这将获得关于非编码RNA如何协调启动和建立感染所需的毒力基因表达的分子机制的重要新信息。

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.