Regulation of Virulence Gene Expression by Regulatory RNA Elements in Yersinia pseudotuberculosis

Abstract

The enteropathogenic bacterium Yersinia pseudotuberculosis produces different sets of virulence factors that guarantee efficient colonization during the early stages, and persistence and dissemination during the late stages of the infection. Alterations of the temperature and the nutrient availability encountered upon host entry and during the ongoing infection lead to global changes of the virulence gene expression profile. Expression of virulence factors (e.g., invasin) that promote colonization and penetration of the intestinal epithelium during the very early phase of the infection is activated by the MarR-type regulator RovA. RovA is a protein thermometer harboring an intrinsic thermosensor. Thermal upshifts to 37°C lead to a reversible conformational change which reduces the DNA binding capacity of the autoactivator and increased susceptibility of RovA for proteolysis by the Lon protease. Furthermore, regulation of rovA expression depends on the post-transcriptional carbon storage regulator system (Csr) implicating the differentially regulated small RNAs CsrB and CsrC and the RNA-binding protein CsrA. Influence of the Csr system occurs through the LysR-type regulator RovM and depends on the nutrient content of the growth medium. After Y. pseudotuberculosis has crossed the intestinal epithelial layer, synthesis of the early virulence genes is repressed and later stage virulence genes, including the type III secretion system and yop genes crucial for immune defense are induced. Activation of these genes is only promoted at 37°C and requires the AraC-like regulator LcrF. Translation of the lcrF mRNA is controlled by a thermoswitch located in the 5′-UTR of the lcrF gene. At moderate temperatures, a stable hairpin structure prevents access of the ribosome and translation of the lcrF mRNA, whereas partial melting of the structure allows ribosome binding at 37°C.