Regulation of Stationary Phase in Escherichia coli

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DESCRIPTION (provided by applicant): Enteric bacteria such as Escherichia coli spend most of their lifetimes starved for one or more essential nutrients. To survive environmental challenges under starvation conditions these bacteria enter a non-growing state called stationary phase. The master regulator of stationary phase is the alternate primary sigma factor RpoS. In rapidly growing cells RpoS levels are low because the orphan response regulator SprE (RssB) targets RpoS for degradation by the CIpP/X protease. We have discovered that when bacteria are starved for carbon, RpoS levels increase because RpoS degradation stops. Starvation for phosphorus also results in elevated levels of RpoS, but in this case levels are elevated because of an increase in rpoS mRNA translation. In contrast starvation for nitrogen does not cause an increase in RpoS levels; rather, RpoS activity is increased. We propose a combination of genetic, biochemical, metabolomic, and computational methods to identify the key signaling and effector molecules that mediate these diverse responses to nutrient deprivation. Since RpoS is known to be important for the pathogenesis of certain bacteria, a detailed understanding of how bacteria enter and exit stationary phase may reveal chinks in the armor of these pathogens. In addition, because the pathways of central metabolism are conserved throughout biology, we think that the signals that trigger transition to a non-growing state may be conserved as well. Thus insights gained in bacteria may shed light on similar processes in eukaryotic microbes, and perhaps animal cells as well.