Adaptive mutations in Shigella and other bacteria

总结：在过去5年中，大肠杆菌的遗传和生物化学研究已经揭示了新的突变，称为适应性突变事件，其仅在特殊的适应性条件下和细菌生长的稳定期以高频率（即通常比对数生长期间发生的突变高3至5个对数）发生。我们最近对志贺氏菌的研究表明，这种生物体也经历了适应性突变，在各种寡糖利用途径和其他代谢和毒力基因区域。 该项目旨在表征志贺菌在各种代谢和毒力基因位点的遗传和生化适应性突变事件的频率和化学性质。将对涉及的基因座进行DNA测序，以检查突变事件的确切性质，重点是理解在稳定期细胞中刺激这些高频（例如10-3）突变事件所涉及的机制。将对其他相关肠道细菌进行类似的研究，以确定适应性突变是否是通过改变生物化学途径或细菌调节其毒力的方法错误识别病原体的原因。

Summary: 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.