The preAB start site does not match those mapped for qseBC in EHEC, which occur at -27 and -78 with respect to the qseB ATG. However, QseB binds to the EHEC qseBC promoter near its transcriptional starts (-27 to -40) but also in a region (-409 to -423) that is located near the transcriptional initiation site we mapped for preAB [21]. We hypothesize that PreA binds to the promoter region of each of these operons (preA-preB, mdaB-ygiN, and ygiW-STM3175) to activate transcription, and future work will define the PreA binding sites in these selleck regulated promoters. It has been previously demonstrated that QseC (PreB ortholog) of EHEC is a receptor for host-derived

epinephrine/norepinephrine and intestinal flora derived AI-3 [5]. In E. coli, QseB positively regulates the transcription of flagellar genes and thus flagellar synthesis and motility. S. Typhimurium motility has also been shown to be affected by norepinephrine and QseC/PreB [6]. However, we were unable to demonstrate a role of PreA/PreB in the regulation of flagellar genes or a role for PreA/PreB in motility, except for an effect of a preB mutation alone. Furthermore, the addition of AI-2 or epinephrine had no effect on wild type motility. Epinephrine did surprisingly increase motility of preA and preAB mutants, but this effect was clearly PreA/PreB independent. Recently, Bearson et al. [22] demonstrated that norepinephrine acts as a siderophore, and that mutations affecting

iron transport no longer responded to norepinephrine. Thus it remains a strong possibility that any effects observed on bacteria by epinephrine/norepinephrine are due to enhanced iron availability. PreB contains a putative iron binding motif in selleck compound its periplasmic region, thus furthering a presumed association of iron with the regulation of PreA/PreB. Though PreA/PreB regulates genes that affect antimicrobial peptide resistance (pmrAB, cptA) and resistance to a variety of drugs (mdaB) or reactive oxygen compounds (e.g. katE, STM1731, dps), none

of the preA or preB mutations affected antimicrobial susceptibility. However, the loss of both preA and preB affected both invasion of epithelial cells in vitro (though no consistant effect of PreA/B on Salmonella Pathogenicity island 1 invasion genes was observed) and virulence in the Thalidomide mouse model. Future work will focus on genes regulated by PreA/PreB that contribute to these phenotypes. Conclusion PreA/PreB is a TCS that regulates Salmonella genes including those of the PmrA/PmrB regulon and those adjacent to preAB on the chromosome. RNA analysis of the genes surrounding preA revealed three PreA-activated operons composed of preA-preB, mdaB-ygiN, and ygiW-STM3175. Though PreA/PreB do not appear to be responsive to Selleck Citarinostat host-derived hormones or microbial quorum-sensing signals as has been previously reported, PreA/PreB do play a role in Salmonella host cell invasion and virulence. Acknowledgements This work was supported by grant AI043521 from the NIH to JSG.