ssrA (tmRNA) plays a role in Salmonella enterica serovar Typhimurium pathogenesis.

Many virulence functions that contribute to in vivo fitness are encoded on pathogenicity islands, sequences presumed to have been acquired by horizontal transfer as evidenced by their atypical base composition and codon usage (17). We have recently used in vivo expression technology (20, 34, 35) to identify several Salmonella enterica serovar Typhimurium in vivo-induced (ivi) acquired sequences, which are distinct within and between Salmonella serovars and contribute to fitness within the host (10). One of these acquired virulence regions, iviXXII, is composed of a mosaic of Salmonella-specific sequences that is also serovar specific (present in a distinct set of serovars of Salmonella but not in E. coli or several other enteric pathogens). Removal of a 17-kb portion of the iviXXII region conferred a greater than 200-fold defect in virulence in a murine model of typhoid fever (10). ssrA resides in or near the junction point of this mosaic of Salmonella-specific sequence (10) and is also known to serve as the insertion site for acquired sequences such as the cryptic phage CP4-57 in Escherichia coli (27) and pathogenicity islands in Vibrio cholerae (25, 30) and Dichelobacter nodosus (2), the causative agents of cholera and ovine foot rot, respectively. ssrA encodes a small, stable RNA molecule (∼350 nucleotides), tmRNA, which may serve as both a tRNA and an mRNA, tagging partially synthesized proteins for degradation (26). Additionally, tmRNA plays other diverse roles in E. coli including regulating an alternative protease activity (27), modulating DNA binding protein activity (41), and contributing to the growth of λ-P22 hybrid phage (40, 55). We investigated whether ssrA contributed to the pathogenesis of Salmonella since ssrA mapped within a 17-kb region that is required for pathogenesis (10) and RNA molecules are also known to play a key role in the virulence of many organisms (17, 39, 43).