Genetic regulation of the twin arginine translocation system in Salmonella enterica serovar Typhimurium

Project SummarySalmonella species cause a range of diseases, from self-limiting gastroenteritis to life-threatening systemicinfections, in a variety of hosts. The CDC estimates that non-typhoid Salmonella species cause 1.2 million casesof foodborne illness and 450 deaths per year in the United States alone. Salmonella enterica serovar Typhimuriumis a leading cause of gastroenteritis worldwide and is used as a model for human typhoid fever in mice. The twinarginine translocation system (Tat) is a protein secretion system that is conserved in bacteria, archaea, and plants.In gram-negative bacteria, it is required for the export of substrate proteins from the cytoplasm to the periplasmof the organism. Tat substrates typically must be properly folded prior to export to the periplasm. In Salmonella,there are about 30 proteins that are substrates of Tat, among these are hydrogenases and amidases. While severalstudies have demonstrated that Tat is required for virulence in Salmonella and other bacterial pathogens, nopublished work has shown regulation of the system and tatABC is thought to be constitutively expressed. Wehave demonstrated that increasing concentrations of bile induce expression of a tatABC-lacZ fusion. Addition of9% bile salt to LB media induces tatABC-lacZ about three-fold. We also have found that deletions of tatABC aremore sensitive than wild type to peptidoglycan targeting antibiotics, though the addition of ampicillin does notactivate expression of tatABC-lacZ. These finding leads to several questions: What is the mechanism of bileactivation of tat expression? What promoter elements are important for expression of tatABC?