GENETIC AND BIOCHEMICAL ANALYSES OF ADAPTIVE MUTATIONS IN SHIGELLA

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Genetic and biochemical studies of Escherichia coli over the past 5 years have revealed novel mutations, termed adaptive mutational events, that occur at high frequency(i.e. generally 3 to 5 logs higher than mutations occurring during logarithmic growth), only under special adaptive conditions, and in the stationary phase of bacterial growth. Our recent studies of Shigella indicate that this organism also undergoes adaptive mutations in a large variety of oligosaccharide utilization pathways and in other metabolic and virulence gene regions. This project is aimed at characterizing genetically and biochemically adaptive mutational events in Shigella at various metabolic and virulence gene loci for frequency and chemical nature. Involved loci will be DNA sequenced to examine the precise nature of the mutational event, with an emphasis on understanding the mechanisms involved in stimulating these high frequency ( e.g. 10-3) mutational events in stationary phase cells. Similar studies of other related enteric bacteria will be conducted to determine if adaptive mutations are a cause of misidentification of pathogens, via altered biochemical pathways, or a method by which bacteria modulate their virulence.