GENETIC AND BIOCHEMICAL ANALYSES OF ADAPTIVE MUTATIONS IN SHIGELLA

近5年来大肠埃希菌的遗传和生化研究 多年来发现了新的突变，称为适应性突变事件， 出现频率较高(即，通常比 在对数生长过程中发生的突变)，仅在特殊情况下 适应条件，并处于细菌生长的稳定期。我们的 最近对志贺氏菌的研究表明，这种生物也经历了 低聚糖利用的多种适应性突变 途径和其他代谢和毒力基因区域。 这个项目的目的是从基因和生物化学的角度来描述 志贺氏菌在不同代谢和时间的适应性突变事件 毒力基因座的频率和化学性质。涉及的基因座将会 进行DNA测序，以检查突变事件的确切性质， 重点是了解刺激的机制 这些处于稳定期的高频(例如10-3)突变事件 细胞。对其他相关肠道细菌的类似研究将在 以确定适应性突变是否是导致 通过改变的生化途径错误识别病原体，或一种 细菌调节其毒力的方法。

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.