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Title: Hydrogen-Stimulated carbon acquisition and conservation in salmonella enterica serovar typhimurium

Author
item LAMICHHANE-KHADKA, REENA - University Of Georgia
item Frye, Jonathan
item PORWOLLIK, STEFFEN - Vaccine Research Instiute Of San Diego
item MCCLELLAND, MICHAEL - Vaccine Research Instiute Of San Diego
item MAIER, ROBERT - University Of Georgia

Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/19/2011
Publication Date: 10/1/2011
Citation: Lamichhane-Khadka, R., Frye, J.G., Porwollik, S., Mcclelland, M., Maier, R.J. 2011. Hydrogen-Stimulated carbon acquisition and conservation in salmonella enterica serovar typhimurium. Journal of Bacteriology. 193(20):5824-5832.

Interpretive Summary: Salmonella enterica serovar Typhimurium is a food borne zoonotic pathogen that causes gastroenteritis in humans. To establish an infection this bacterium must compete successfully with the host microflora in the intestine during colonization. Salmonella is unique in that it can utilize molecular hydrogen, an abundant molecule in the host intestine, as an energy source for growth. However, very little is known about how Salmonella uses hydrogen. We used microarray analysis to identify gene expression changes during exposure to H2 gas in Salmonella. Genes up-regulated by H2 include those that encode proteins involved in the transport of amino acids (artI, artP, glnH, glnP, glnQ) and sugars (rbsB, mglB, ugpB, manX, manY, nagE). Genes involved in carbon conservation (aceA) and (aceB) were also up regulated and strains with deletion of either aceA or aceB showed reduced H2-dependent growth compared to the wild type. Hydrogen stimulates the expression of genes involved in nutrient and carbon acquisition and in carbon-conserving pathways, linking carbon and energy metabolism to sustain H2-dependent growth. H2 metabolism enables Salmonella to compete with the host flora and establish an infection and could be targeted for disease prevention.

Technical Abstract: Salmonella enterica serovar Typhimurium can utilize molecular hydrogen for growth and amino acid transport during anaerobic growth. Via microarray we identified H2 gas-affected gene expression changes in Salmonella. Addition of H2 caused altered expression of 965 genes; 176 genes were H2-up-regulated and 789 were H2-down-regulated. The significantly H2-up-regulated genes include those that encode proteins involved in the transport of iron (fhuA, fhuF, sitA, sitB, sitC, yciE, yciF) amino acids (artI, artP, glnH, glnP, glnQ) nucleosides (pnuC) and sugars (rbsB, mglB, ugpB, manX, manY, nagE). Genes encoding isocitrate lyase (aceA) and malate synthase (aceB), both involved in the C-conserving glyoxylate pathway, and genes encoding enzymes of the D-glycerate pathway (garK, garR, garL) were significantly up-regulated in cells with H2. Mutant strains with deletion of either aceA or aceB showed reduced H2-dependent growth compared to the wild type. Genes encoding glutamine-specific transporters (GlnH, P, Q) were up-regulated by H2, and cells pre-grown with H2 showed 1.5-fold increased 14C-glutamine uptake. Similarly, the mannose-uptake system genes manX and manY were up-regulated by H2, and cells pre-grown with H2 showed approximately 2.0-fold increased 14C-mannose uptake compared to the cells grown in absence of H2. Hydrogen stimulates the expression of genes involved in nutrient and carbon acquisition and in carbon-conserving pathways, linking carbon and energy metabolism to sustain H2-dependent growth.