Characterization of the Bacterial Stress Response Network

点击翻译按钮获取中文摘要

Bacteria use signal transduction pathways to sense and adapt to environmental changes. Each pathway contains a sensing element and a response element that leads to changes in adaptive gene expression. The flow of information through an individual signaling pathway from the environment through to a response is well understood in many cases, however signaling pathways are also linked by complex, diverse connections that lead to the formation of an exquisitely sensitive signaling network. Although poorly understood, two types of connection have been identified. A given signaling pathway may be linked to others in the cell because it regulates the transcription or translation of genes that encode another signaling pathway. Additionally, one signaling pathway may control the expression of proteins that directly impact the activities of another. My group recently showed that the Escherichia coli envelope stress response demonstrates connections of both types, to multiple other stress responses. For example, envelope stress leads to changes in the expression of proteins that impact the activities of other stress responsive sensor kinase proteins. Envelope stress also changes the transcription levels of small RNAs (sRNAs) that regulate the translation of the general stress response transcription factor sS and the osmolarity stress regulators EnvZ and OmpR. Intriguingly, envelope stress also leads to changes in expression of uncharacterized putative sRNAs and transcription factors. I hypothesize that uncharacterized envelope stress regulated sRNAs and transcription factors form part of the microbial stress response network and contribute to stress adaptation. We will use bioinformatic, genomic, genetic, and biochemical approaches to characterize these regulators and identify new connections important for the formation of an exquisitely sensitive, integrated, E. coli stress response network. We will begin to address our long-term goal of extending our analyses to all known signaling pathways in E. coli in order to outline a comprehensive signaling network controlling cellular behavior.