Transcriptional analysis of Salmonella enterica serovar Typhimurium (S. Typhimurium) in the presence of the mammalian hormone norepinephrine revealed up-regulation of genes in the flagellar and chemotaxis regulon. Motility assays confirmed enhanced motility of wild-type S. Typhimurium in the presence of norepinephrine that could be blocked by the alpha-adrenergic antagonist, phentolamine. Furthermore, a mutation in the qseC gene, encoding the sensor kinase of the two-component QseBC quorum-sensing system, also diminished motility of S. Typhimurium. To investigate the role of S. Typhimurium QseC in vivo, 13-week old pigs were intranasally inoculated with equal concentrations (1 x 10(9)CFU) of wild-type S. Typhimurium and a qseC mutant. Over a 1-week competitive index experiment, the qseC mutant displayed decreased colonization of the gastrointestinal tract compared to the wild-type parent strain. Thus, this study has identified a role for the QseBC quorum-sensing signal transduction system in motility and swine colonization of S. Typhimurium. Cross-talk between cell-cell communication systems in Salmonella (quorum sensing) and host hormones may explain opportunistic behaviors of the pathogen, such as immune evasion and stress-induced recrudescence of Salmonella, during fluctuations of host hormone levels.