Stringent Response Regulators Contribute to Recovery from Glucose Phosphate Stress in Escherichia Coli

In enteric bacteria such as , the transcription factor SgrR and the small RNA SgrS regulate the response to glucose phosphate stress, a metabolic dysfunction that results in growth inhibition and stems from the intracellular accumulation of sugar phosphates. SgrR activates the transcription of , and SgrS helps to rescue cells from stress in part by inhibiting the uptake of stressor sugar phosphates. While the regulatory targets of this stress response are well described, less is known about how the SgrR-SgrS response itself is regulated. To further characterize the regulation of the glucose phosphate stress response, we screened global regulator gene mutants for growth changes during glucose phosphate stress. We found that deleting , which encodes a regulator of the stringent response to nutrient starvation, decreases growth under glucose phosphate stress conditions. The stringent response alarmone regulator ppGpp (synthesized by RelA and SpoT) also contributes to recovery from glucose phosphate stress: as with , mutating and worsens the growth defect of an mutant during stress, although the mutant defect was only detectable under lower stress levels. In addition, mutating or and lowers expression (as measured with a P - fusion), suggesting that the observed growth defects may be due to decreased induction of the glucose phosphate stress response or related targets. This regulatory effect could occur through altered transcription, as and mutants also exhibit decreased expression of a P - fusion. Taken together, this work supports a role for stringent response regulators in aiding the recovery from glucose phosphate stress. Glucose phosphate stress leads to growth inhibition in bacteria such as when certain sugar phosphates accumulate in the cell. The transcription factor SgrR and the small RNA SgrS alleviate this stress in part by preventing further sugar phosphate transport. While the regulatory mechanisms of this response have been characterized, the regulation of the SgrR-SgrS response itself is not as well understood. Here, we describe a role for stringent response regulators DksA and ppGpp in the response to glucose phosphate stress. and mutants exhibit growth defects under glucose phosphate stress conditions. These defects may be due to a decrease in stress response induction, as deleting or and also results in decreased expression of and This research presents one of the first regulatory effects on the glucose phosphate stress response outside SgrR and SgrS and depicts a novel connection between these two metabolic stress responses.