The enteric pathogens Salmonella enterica and E. coli 0157:H7 face daunting odds during their voyages in the natural environment and through an infected host. They must manage stresses ranging from feast to famine, acid to base, and high to low osmolarity, among others.
Our laboratory has discovered critical adaptive responses of Salmonella and E. coli O157:H7 that contribute to the survival of these pathogens in acidic environments ranging from stomach acidity to fused phagolysosomes in infected macrophages. These adaptive responses are induced when cells are shifted to mild acid conditions but, once engaged, protect the organisms against strong acid conditions. We are investigating these responses at the biochemical, genetic and molecular levels.
Although Salmonella and Escherichia are closely related microbes, E. coli has evolved three systems of acid resistance superior to that of Salmonella. These mechanisms are responsible for the low infectious dose characteristic of E. coli 0157. Determining how these mechanisms enable cells to cope more efficiently with acid stress is a major focus of our laboratory. We are asking how cells "sense" the change in proton concentration during adaptation, and subsequently transmit that signal to the transcriptional/translational machinery. Our main goal is to use these findings to understand the response of bacteria to hostile environments, both natural and human. Results will provide new insights into how cells control their internal pH, repair damage to macromolecules, and modulate gene expression upon recognizing a Aclear and present danger@ to survival.
Audia, JP, CC Webb and JW Foster. 2001. Breaking through the acid barrier: an orchestrated response to proton stress by enteric bacteria. Int. J. Med Microbiol. 291:1-10.
Moreno, M., J. Audia, C. Webb, S. Bearson and John W. Foster. 2000 Regulation of Sigma S degradation in Salmonella enterica var Typhimurium: in vivo interactions between Sigma S, the response regulator MviA/RssB, and ClpX. J. Mol. Microbiol Biotech. 2:245-254.
Bang, Iel Soo, B. H. Kim, J. W. Foster and Y. K. Park. 2000. OmpR Regulates the Stationary Phase Acid Tolerance Response of Salmonella enterica Var Typhimurium. J. Bacteriol. 182:2245-2252.
M-P. Castanie-Cornet, T. Penfound, D. Smith, J. F. Elliott, and J. W. Foster. 1999. Control of acid resistance in Escherichia coli. J. Bacteriol. 181:3525-3535.
F. C. Fang, M. A. DeGroote, J. W. Foster, A. Baumler, U. Ochsner, T. Testerman, S. Bearson, J-C. Giard, Y. Xu, G. Campbell, and T. Laessig. 1999. Virulent Salmonella typhimurium has two periplasmic Cu, Zn-Superoxide dismutase. Proc. Natl. Acad. Sci. 96:7502-7507.
C. Webb, M. Moreno, M. Wilmes-Reisenberg, R. Curtiss III, and J. W. Foster. 1999. Effects of ClpXP protease and DksA in Sigma S production and Virulence in Salmonella typhimurium. Mol. Microbiol. 34:112-123.
J. W. Foster. 1999. When protons attack: Microbial strategies of acid tolerance. Current Opinion Microbiol. 2:170-174.
T. Penfound and J. W. Foster. 1999. NAD-dependent DNA-binding activity of the bifunctional NadR regulator of Salmonella typhimurium. J. Bacteriol. 181:648-655.
| Phone: | (251) 460-6323 | |
|---|---|---|
| FAX: | (251) 460-7931 | |
| E-mail: | fosterj@sungcg.usouthal.edu |
Robert
N. Lausch