We are studying how Salmonella thrives in the host environment. We are currently focusing on three projects:
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 flora and use this information to adjust its gene expression accordingly. Surprisingly, we discovered that the normal gut flora does not make AHLs and instead, Salmonella is detecting the AHL production of other pathogens in the gut. Salmonella can detect the AHL production ofAeromonas 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.
Coordination of metabolism and virulence by SirA and CsrA
Throughout the gamma-proteobacteria a two-component response regulatory system determines the metabolic state of the cell and regulates gene expression accordingly. BarA is the histidine sensor kinase that detects the metabolic signal (probably acetate which peaks in late exponential phase) and SirA is the transcription factor that is phosphorylated and activated by BarA. A second system is the Carbon Storage Regulatory system that consists of an RNA binding protein that binds and prevents translation of particular mRNAs. Interestingly, SirA activates the expression of two small RNAs that inhibit CsrA activity. Currently, we are studying when SirA and CsrA become active during various stages of infection.
Characterization of fructose-asparagine metabolism
We recently determined that Salmonella relies heavily on a single nutrient during growth in the inflamed intestine, fructose-asparagine. We are characterizing the enzymology and regulation of this system as well as developing novel therapeutic approaches that target this system.
Ali MM, Newsom DL, Gonzalez JF, Sabag-Daigle A, Stahl C, Steidley B, Dubena J, Dyszel JL, Smith JN, Dieye Y, Arsenescu R, Boyaka PN, Krakowka S, Romeo T, Behrman EJ, White P & Ahmer BMM. 2014. Fructose-asparagine is a primary nutrient during growth of Salmonella in the inflamed intestine. PLOS Pathogens 10(6): e1004209.
Habyarimana F, Sabag-Daigle A & Ahmer BMM. 2014. The sdiA-regulated gene srgE encodes a type III secreted effector. Journal of Bacteriology 196:2301-2312. Habyarimana F, Swearingen MC, Young GM, Seveau S & Ahmer BMM. 2014. Yersinia enterocolitica inhibits Salmonella enterica and Listeria monocytogenes cellular uptake. Infection and Immunity 82:174-183. Swearingen MC, Sabag-Daigle A & Ahmer BMM. 2013. Are there acyl-homoserine lactones within mammalian intestines? Journal of Bacteriology 195:173-179. Sabag-Daigle A & Ahmer BMM. 2012. ExpI and PhzI are descendants of the long lost cognate signal synthase for SdiA. PLOS ONE 7(10):e47720. Sabag-Daigle A, Soares JA, Smith JN, Elmasry ME & Ahmer BMM. 2012. The acyl-homoserine lactone (AHL) receptor, SdiA, of E. coli and Salmonella does not respond to indole. Applied and Environmental Microbiology 78:5424-5431. Swearingen MC, Porwollik S, Desai PT, McClelland M & Ahmer BMM. 2012. Virulence of 32 Salmonella strains in mice. PLOS ONE 7(4): e36043. Soares JA & Ahmer BMM. 2011. Detection of acyl-homoserine lactones by Escherichia and Salmonella. Current Opinion in Microbiology 14(2):188-193. Ahmer BMM & Gunn JS. 2011. Interaction of Salmonella spp. with the intestinal microbiota. Frontiers in Microbiology 2:101.
Dyszel JL, Smith JN, Lucas DE, Soares JA, Swearingen MC, Vross MA, Young GM & Ahmer BMM
. (2010) Salmonella enterica
serovar Typhimurium can detect acyl homoserine lactone production by Yersinia enterocolitica
in mice. Journal of Bacteriology 192
The all-time favorite:
- Ali MM, Newsom DL, Gonzalez JF, Sabag-Daigle A, Stahl C, Steidley B, Dubena J, Dyszel JL, Smith JN, Dieye Y, Arsenescu R, Boyaka PN, Krakowka S, Romeo T, Behrman EJ, White P, & Ahmer BMM. 2014. Fructose-asparagine is a primary nutrient during growth of Salmonella in the inflamed intestine. PLOS Pathogens10(6): e1004209.