الفهرس 
AbstractOnly 14 pages are availabe for public view
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Abstract
The normal microbiota is critically important for protecting its host from pathogens. The mechanisms by which pathogens interact with and survive among the normal microbiota are largely unknown. We used a genetic screening technique known as Transposon Site Hybridization (TraSH) in gnotobiotic mice to identify those genes of Salmonella that are important in the presence of a single member of the microbiota, Enterobacter cloacae. Five genes were identified that are more important for fitness in the presence of E. cloacae (germ-free mice mono-associated with E. cloacae) than in its absence (germ-free mice). Two genes encode the two-component signal transduction system SirA/BarA that regulates the carbon storage regulatory system to coordinate metabolism and virulence. Three genes are found within a previously uncharacterized five gene horizontally acquired locus that - based on homology studies - seems to play a role in the acquisition and utilization of a certain nutrient source (STM3598 to STM3602). We have determined that Salmonella uses this locus for the uptake and utilization of a novel nutrient, fructose-asparagine (F-Asn). We suggest that this locus be named fra based on its function. This locus is critical for Salmonella fitness in the inflamed intestine, but is not of benefit if Salmonella cannot initiate inflammation (a SPI1 SPI2 double mutant) or cannot use tetrathionate as a terminal electron acceptor during iii anaerobic respiration (a ttrA mutant). This study adds to recent findings that Salmonella outcompetes the normal microbiota by initiating inflammation, which disrupts the microbiota and leads to the creation of the terminal electron acceptor tetrathionate after oxidation of endogenous thiosulphates by the reactive oxygen species that are released during the inflammatory process. Salmonella then uses tetrathionate to respire anaerobically on a select few carbon sources including ethanolamine and F-Asn. The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies.