Professor, Microbial Infection and Immunity
We are studying how Salmonella thrives in the host environment. We are currently focusing on three projects:
1. Detection of other microbes by Salmonella.
Some bacteria use pheromones (N-acylhomoserine lactones or AHLs) to determine their population density. Salmonella does not make AHLs but it can detect the AHLs produced by other bacteria. We hypothesized that Salmonella would detect AHLs made by the normal intestinal microbiota and use this information to adjust its gene expression accordingly. Surprisingly, we discovered that the normal gut microbiota does not make AHLs and instead, Salmonella is detecting the AHL production of other pathogens in the gut. Salmonella can detect the AHL production of Aeromonas hydrophila in turtles and Yersinia enterocolitica in mice. We are characterizing this same AHL detection system in E. coli, Klebsiella, Enterobacter and other closely related organisms.
2. Characterization of fructose-asparagine metabolism.
We recently discovered that fructose-asparagine is a nutrient for Salmonella in the inflamed intestine. We are characterizing the enzymology and regulation of this system. During these studies we determined that inhibition of the FraB enzyme in the pathway causes the accumulation of a metabolite that is toxic to Salmonella. This makes FraB an interesting drug target. We are actively screening compounds to find inhibitors of FraB. Future projects include determining why fructose-asparagine is toxic to a Salmonella fraB mutant (what is the mechanism of intoxication?) and determining how Salmonella recovers from these effects and how Salmonella might become resistant to FraB inhibitors
3. A multi-omics approach to studying infection.
We are starting a new project in collaboration with the Kelly Wrighton and Vicki Wysocki labs in which we characterize Salmonella infection of the mouse using several omics technologies. We will characterize the effect of Salmonella on the intestinal microbial community using 16S profiling and shotgun metagenomics; we will characterize the gene expression of Salmonella and the rest of the community using metatranscriptomics; and we will characterize the metabolites in the system using metabolomics. This will all be done at multiple time points to obtain a dynamic view of the infection. Integration of this data will generate large numbers of testable hypotheses. Future projects will include testing these hypotheses by constructing Salmonella mutants to see how they behave in various mouse models, including gnotobiotic mouse models (mice with a defined microbial community composition).
710 Biomedical Research Tower (BRT)
460 W 12th Ave, Columbus OH 43210