Salmonella species cause a range of diseases, from self-limiting gastroenteritis to life-threatening systemic infections, in a variety of hosts. The CDC estimates that non-typhoid Salmonella species cause 1.2 million cases of foodborne illness and 450 deaths per year in the United States alone. Salmonella enterica serovar Typhimurium is a leading cause of gastroenteritis worldwide and is used as a model for human typhoid fever in mice. The twin arginine 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 periplasm of 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 several studies have demonstrated that Tat is required for virulence in Salmonella and other bacterial pathogens, no published work has shown regulation of the system and tatABC is thought to be constitutively expressed. We have demonstrated that increasing concentrations of bile induce expression of a tatABC-lacZ fusion. Addition of 9% bile salt to LB media induces tatABC-lacZ about three-fold. We also have found that deletions of tatABC are more sensitive than wild type to peptidoglycan targeting antibiotics, though the addition of ampicillin does not activate expression of tatABC-lacZ. These finding leads to several questions: What is the mechanism of bile activation of tat expression? What promoter elements are important for expression of tatABC?

Public Health Relevance

Salmonella enterica serovar Typhimurium is a leading cause of gastroenteritis worldwide and is used as a model for human typhoid fever in mice. The twin arginine translocation (Tat) system is a protein secretion system that is required for the translocation of about 30 proteins in Salmonella, including proteins required for biogenesis of the cell wall. Our work is relevant to public health because it will lead to a better understanding of environmental factors that impact production of bacterial cell wall components and may lead to alternative treatments for severe Salmonellosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI144661-03
Application #
9844930
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Alexander, William A
Project Start
2019-06-19
Project End
2020-12-31
Budget Start
2020-01-01
Budget End
2020-12-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Midwestern University (Glendale AZ)
Department
Physiology
Type
Schools of Osteopathic Medicine
DUNS #
963264320
City
Glendale
State
AZ
Country
United States
Zip Code
85308