Durfee Tim, Hansen Anne-Marie, Zhi Huijun, Blattner Frederick R, Jin Ding Jun
Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Bacteriol. 2008 Feb;190(3):1084-96. doi: 10.1128/JB.01092-07. Epub 2007 Nov 26.
The bacterial stringent response serves as a paradigm for understanding global regulatory processes. It can be triggered by nutrient downshifts or starvation and is characterized by a rapid RelA-dependent increase in the alarmone (p)ppGpp. One hallmark of the response is the switch from maximum-growth-promoting to biosynthesis-related gene expression. However, the global transcription patterns accompanying the stringent response in Escherichia coli have not been analyzed comprehensively. Here, we present a time series of gene expression profiles for two serine hydroxymate-treated cultures: (i) MG1655, a wild-type E. coli K-12 strain, and (ii) an isogenic relADelta251 derivative defective in the stringent response. The stringent response in MG1655 develops in a hierarchical manner, ultimately involving almost 500 differentially expressed genes, while the relADelta251 mutant response is both delayed and limited in scope. We show that in addition to the down-regulation of stable RNA-encoding genes, flagellar and chemotaxis gene expression is also under stringent control. Reduced transcription of these systems, as well as metabolic and transporter-encoding genes, constitutes much of the down-regulated expression pattern. Conversely, a significantly larger number of genes are up-regulated. Under the conditions used, induction of amino acid biosynthetic genes is limited to the leader sequences of attenuator-regulated operons. Instead, up-regulated genes with known functions, including both regulators (e.g., rpoE, rpoH, and rpoS) and effectors, are largely involved in stress responses. However, one-half of the up-regulated genes have unknown functions. How these results are correlated with the various effects of (p)ppGpp (in particular, RNA polymerase redistribution) is discussed.
细菌严谨反应是理解全局调控过程的一个范例。它可由营养物质下调或饥饿引发，其特征是警报素（p）ppGpp迅速依赖RelA增加。该反应的一个标志是从促进最大生长的基因表达向生物合成相关基因表达的转变。然而，大肠杆菌中伴随严谨反应的全局转录模式尚未得到全面分析。在此，我们展示了两种丝氨酸羟肟酸盐处理培养物的基因表达谱时间序列：（i）MG1655，一种野生型大肠杆菌K-12菌株，以及（ii）一种在严谨反应中存在缺陷的同基因relAΔ251衍生物。MG1655中的严谨反应以分级方式发展，最终涉及近500个差异表达基因，而relAΔ251突变体反应在时间上延迟且范围有限。我们表明，除了稳定RNA编码基因的下调外，鞭毛和趋化性基因表达也受到严谨控制。这些系统以及代谢和转运蛋白编码基因转录的减少构成了大部分下调的表达模式。相反，上调基因的数量明显更多。在所使用的条件下，氨基酸生物合成基因的诱导仅限于衰减子调控操纵子的前导序列。相反，具有已知功能的上调基因，包括调节因子（如rpoE、rpoH和rpoS）和效应器，大多参与应激反应。然而，上调基因中有一半具有未知功能。本文讨论了这些结果如何与（p）ppGpp的各种效应（特别是RNA聚合酶重新分布）相关联。
