Signal integration by the two-component signal transduction response regulator CpxR

Department of Microbiology and Immunology, 2160 S. First Ave. Bldg. 105, Maywood, IL 60153

^* To whom correspondence should be addressed. Email: awolfe{at}lumc.edu.

	Abstract

The CpxAR two-component signal transduction system in Escherichia coli and other pathogens senses diverse envelope stresses and promotes the transcription of a variety of genes that remedy these stresses. An important member of the CpxAR regulon is cpxP. The CpxA-dependent transcription of cpxP has been linked to stresses such as misfolded proteins and alkaline pH. It also has been proposed that acetyl phosphate, the intermediate of the Pta-AckA pathway, can activate the transcription of cpxP in a CpxA-independent manner by donating its phosphoryl group to CpxR. We tested this assumption by measuring the transcription of cpxP in mutants of the CpxAR pathway, mutants of the Pta-AckA pathway, and a combination of both. From this epistasis analysis, we learned that CpxR integrates diverse stimuli. Those that originate in the envelope depend on CpxA, while those associated with growth and central metabolism depend on the Pta-AckA pathway. While CpxR could receive a phosphoryl group from acetyl phosphate, this global signal was not the primary trigger for CpxR activation associated with the Pta-AckA pathway. On the strength of these results, we contend that the interplay between central metabolism and signal transduction can be quite complex and that successful investigations of such interactions must include a complete epistatic analysis.