Genetic and Environmental Mediators of Salmonella Infection

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Title: Genetic and Environmental Mediators of Salmonella Infection
Author: Huang, Yanyan
Advisors: Paul Orndorff, Committee Member
Craig Altier, Committee Co-Chair
Wondwossen A. Gebreyes, Committee Member
Jay F. Levine, Committee Co-Chair
Abstract: The purpose of the research is to identify genetic determinants and environmental signals of infection in Salmonella enterica serovar Typhimurium. We established pigs as an animal model to identify Salmonella genes specifically expressed in vivo by using a recombinase-based in vivo expression system. A total of 55 clones from a genomic library of ˜ 10,000 random Salmonella DNA fragments were isolated from the tonsils and small intestinal tracts of pigs. Characterization of in vivo induced genes by sequencing showed that genes involved in adhesion, colonization, virulence, stress response, and a two-component regulator were specifically induced after infection of pigs. High temperature and osmolarity induced a number of these in vivo expressed genes. We identified formate as an environmental signal that induces invasion gene expression in Salmonella. The effect of formate required a pH below neutrality, and we found that the distal ileum of mice had the appropriate formate concentration and pH to elicit invasion of Salmonella. We further found that formate plays a role in inducing invasion gene expression by changing carbon flux. To identify the formate regulon, Salmonella DNA microarrays were employed to compare gene expression of wild type Salmonella grown with or without formate. A part of formate hydrogenlyase complex, encoded by the hyc operon, was induced by the additional formate. A large class of genes involved in the respiratory electron transfer system was also affected by formate. Nitrate reductase and succinate dehydrogenase were repressed, while fumarate reductase was induced by formate. Thus, in the presence of formate, fumarate may be a more preferred electron acceptor than nitrate. A number of genes involved in vitamin B12 synthesis, aromatic acid synthesis, flagella synthesis, lipopolysaccharide synthesis, and two-component regulators were also affected by formate. Surprisingly, genes affected by formate overlapped with some in vivo induced genes, suggesting that formate present in the distal ileum could be a signal for Salmonella infection of animal hosts.
Date: 2007-11-08
Degree: PhD
Discipline: Comparative Biomedical Sciences

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