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Abstract
Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium) is a significant food borne pathogen causing gastroenteritis in humans. Although there has been extensive research conducted on S. Typhimuriums pathogenicity islands and effector proteins, the potential role of S. Typhimuriums metabolic genes in colonization has been widely overlooked until recently. In recent studies, a number of metabolic genes have been implicated as important for successful colonization of chickens, pigs, and calves. RpoN is an alternative sigma factor required for transcription of genes involved in a range of metabolic pathways including nitrogen metabolism, H2 evolution and uptake, carbohydrate transport and degradation of aromatic compounds. The RpoN regulon in Salmonella is not fully characterized. Many RpoN-dependent genes are of unknown function, all of which appear to be involved in metabolism. The goal of my research has been to characterize genes within the RpoN regulon. S. Typhimurium possesses three sugar phosphotransferase (PTS) permeases which are absent in most strains of closely related bacteria and whose expression is controlled by the transcription factor RpoN. S. Typhimurium strains lacking all three of these PTS permeases or the activators responsible for their transcription weredeficient in colonization of the chicken ileum, jejunum, and ceca. I identified the substrates for two of the three PTS permeases. The permease and associated enzymes encoded with the dga locus are responsible for the transport and utilization of D-glucosaminate. The permease and associated enzymes encoded within the gfr locus are responsible for the transport and utilization of fructoselysine and glucoselysine. It is possible that D-glucosaminate, fructoselysine, and/or glucoselysine may be encountered by S. Typhimurium in the gastrointestinal tract of chickens and other animals. Two other RpoN-dependent operons have been looked at that also seem to be involved in metabolism. The first may be involved in arginine transport or utilization and may have broader effects such as involvement in acid stress. The other operon appears to be important for gluconate utilization during anaerobic conditions. Taken together, the five RpoN-dependent operons discussed here are an example of the diversity of metabolic genes in the RpoN regulon.