Whether within the host or in the external environment, enteric bacteria often survive under conditions that do not support exponential growth. One factor frequently preventing growth is starvation for a carbon and energy source (C-starvation). Upon encountering such conditions, Salmonella enterica serovar Typhimurium (S. Typhimurium) undergoes a series of changes in global gene expression and physiology that we refer to is the Starvation-Stress Response (SSR). The SSR results in a cell that is capable of surviving continued, long-term starvation and exposure to a variety of other stresses. Previously, we discovered that the SSR is partially regulated by the alternate sigma factor, sigma(E), encoded by the rpoE gene. We showed that sigma(E) is activated and accumulates during C-starvation and that rpoE is essential for long-term C-starvation survival and for C-starvation-induced cross-resistances. Sigma(E)-type sigma factors control the expression of extra-cytoplasmic functions. However, the genes regulated by such sigma factors varies greatly depending upon the bacterial species. Our preliminary data indicates that the set of genes regulated by sigma(E) during C-starvation in S. Typhimurium is very different from the rpoE-regulon of E. coli reported in the literature. Therefore, our first goal is to identify S. Typhimurium genes induced in response to C-starvation in a sigma(E)-dependent manner. A few of the more interesting genes (e.g., genes unique to Salmonella) will be chosen for further characterization. Using knock-out mutants, we will determine the role of each gene in long-term C-starvation survival and in C-starvation-induced cross-resistance to high temperature, low pH, oxidizing agents, and antimicrobial compounds. In addition, we will further investigate the regulation of these genes by other known stress response regulators such as cAMP-CRP, ppGpp, sigma(S), Lrp, OxyR, SoxRS, Fnr, ArcAB, PhoPQ, and PmrAB. Through our collaboration with Dr. Mark Roberts (Univ. of Glasgow), we will determine the role of these sigma(E)-SSR genes in mouse virulence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AI060759-01
Application #
6806186
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Alexander, William A
Project Start
2004-07-01
Project End
2008-06-30
Budget Start
2004-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$210,000
Indirect Cost
Name
University of South Alabama
Department
Other Basic Sciences
Type
Schools of Allied Health Profes
DUNS #
172750234
City
Mobile
State
AL
Country
United States
Zip Code
36688