Posttranscriptional Regulation of Type III Secretion in Yersinia

The three pathogenic Yersinia species that can cause disease in humans and animals have a high degree of genetic similarity, which allows us to study the evolution of virulence gene regulation. Bacterial small, noncoding RNAs (sRNAs) participate in the posttranscriptional regulation of gene expression, often by affecting protein translation or transcript stability. Many trans-encoded sRNAs require the RNA-binding chaperone protein Hfq to stabilize the interaction with their mRNA targets. Recent studies have demonstrated that Hfq contributes to the pathogenesis of a number of bacterial species, suggesting that sRNAs play an essential role in the regulation of virulence. However the role of Hfq and sRNAs has not been investigated thoroughly in the Yersinia species.;I have shown that a Deltahfq mutant of Yersinia pseudotuberculosis is deficient in its ability to cause mortality in an intragastric mouse model of infection, and is attenuated 1,000-fold compared to the parental strain. Hfq is also required for virulence through the intraperitoneal route of infection and for persistence of the bacterium in the Peyer's patches, mesenteric lymph nodes, and spleen, suggesting a direct role for Hfq in systemic infection. Furthermore, the Delta hfq mutant of Y. pseudotuberculosis has decreased production of type III secretion system (T3SS) effector proteins.;The pathogenic Yersinia species require the conserved Yop-Ysc T3SS for pathogenesis. This T3SS delivers 7 effector proteins from the bacteria into host cells, and the effectors enable Yersinia to subvert the host innate immune system. T3SS regulation in Yersinia is tightly controlled at each step from transcription to translocation, however, the contribution of sRNAs to its regulation has been largely unstudied. Here, Hfq is shown to be similarly required for the posttranscriptional regulation of the T3SS in Yersinia pestis as was seen for Y. pseudotuberculosis. Additionally, a Yersinia-specific sRNA, Ysr141, carried on the T3SS-encoding plasmid pCD1, is required for the production of multiple T3SS proteins in Y. pestis. Ysr141 also specifically activates the translation of the T3SS effector protein YopJ. This is the first example of a specific sRNA involved in the regulation of the T3SS in Yersinia, adding another layer to the already complex regulation of this system.