James M. Slauch
Associate Professor of Microbiology
Program Director, Medical Scholars Program
slauch@uiuc.edu
B.S. (Biochemistry), The Pennsylvania State University, 1984
Ph.D. (Molecular Biology), Princeton University, 1990
Postdoc. (Microbiology), Harvard Medical School, 1990-1993
Molecular mechanisms of Salmonella pathogenesis
Salmonella cause 1.4 million cases of gastroenteritis and enteric fever per year in the US and lead all other foodborne bacterial pathogens as a cause of death. The long-term objectives of our research are to understand the molecular mechanisms by which Salmonella circumvents the host immune system to cause disease. Salmonellatyphimurium provides an ideal model system to study molecular pathogenesis. The genetics of this organism are well defined and allow the simple manipulation and characterization of mutations that affect virulence. In addition, there is an excellent animal model of infection to study the effects of bacterial mutations on pathogenesis. It has been our goal to take full advantage of the genetic power of the system in our pathogenic studies.
The most serious Salmonella disease results from extraintestinal infection and bacteremia. Children, the elderly, and immunocompromised individuals are particularly susceptible to more serious Salmonella infection. The hallmark of these extraintestinal infections is the ability of Salmonella to survive in macrophages, which normally kill bacteria by producing a variety of antimicrobials, including superoxide (O 2 -) and other reactive oxygen and nitrogen species. Evidence that phagocyte-produced superoxide is important in Salmonella infection is clear; mice and humans who are genetically defective in superoxide production are significantly more susceptible to infection. However, the molecular mechanism by which external superoxide kills or inhibits Salmonella is not known. Is the target of superoxide in the periplasm or the outer surface of the inner membrane, or is the target intracellular?
S. typhimurium resistance to the oxidative burst of phagocytes requires periplasmic Copper/Zinc co-factored superoxide dismutase (SodC), which detoxifies superoxide. The S. typhimurium strain that we study produces two separate periplasmic superoxide dismutases. SodCII is chromosomally encoded, whereas SodCI is encoded on the fully functional bacteriophage Gifsy-2. We have shown that sodCI mutants are 6-7 fold reduced in virulence as compared to the wild type strain. In contrast SodCII is not required during infection, even in the absence of SodCI.
These data leave us with a paradox. We have shown that both SodCI and SodCII are produced during infection. However, only SodCI is capable of contributing to virulence. We are using a variety of genetic and biochemical techniques to understand the relative expression SodCI and SodCII in vitro and during infection, and the biochemical differences between the two enzymes that would lead to differential roles in pathogenesis. We also have several projects to determine the targets of superoxide and the mechanism of bacterial inhibition.
Our second are study is the regulation of the Type III Secretion System (T3SS) encoded on Salmonella Pathogenicity Island 1 (SPI1). This complex of over 30 proteins is transcriptionally induced in response to a variety of environmental signals such that the machinery is produced at the appropriate time in the intestine of the host. Using this machine, Salmonella injects bacterial proteins, termed effectors, into the epithelial cells leading to actin rearrangement and invasion of the bacterium. Using careful genetic analyses, we have modeled the complex circuitry responsible for integrating these various environmental signals.
Ellermeier, C.D., Ellermeier, J.R., and Slauch, J.M. (2005) “HilD, HilC, and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonellaenterica serovar Typhimurium,” Mol. Microbiol. 57:691-705. [Abstract]
Ikeda, J.S., Janakiraman, A., Kehres, D.G., Maguire M.E., and Slauch, J.M. (2005) “Transcriptional regulation of sitABCD of Salmonellaenterica serovar Typhimurium by MntR and Fur,” J. Bacteriol. 187:912-922. [Abstract]
Krishnakumar, R., Craig, E.M., Imlay, J.A., and Slauch, J.M. (2004) “Physical properties allow SodCI but not SodCII to contribute to virulence in Salmonellaenterica serovar Typhimurium strain 14028,” J. Bacteriol. 186:5230-5238. [ Abstract]
Ellermeier, C.D., and Slauch, J.M. (2004) “RtsA coordinately regulates DsbA and the Salmonella pathogenicity island 1 type three secretion system,” J. Bacteriol. 186:68-79. [ Abstract]
Ellermeier, C.D., and Slauch, J.M. (2003) “RtsA and RtsB coordinately regulate expression of the invasion and flagellar genes in Salmonella enterica serovar Typhimurium,” J. Bacteriol. 185: 5096-5108. [ Abstract]
Ellermeier , C.D., Janakiraman, A., and Slauch, J.M. (2002) “Construction of targeted single copy lac fusions using l Red and FLP-mediated site-specific recombination in bacteria,” Gene 290: 153-161. [ Abstract]
View James M. Slauch's Publications at the National Library of Medicine (PubMed)