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Journal of Bacteriology, April 2008, p. 2314-2322, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01906-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Signal Integration by the Two-Component Signal Transduction Response Regulator CpxR{triangledown}

Alan J. Wolfe,* Niyati Parikh, Bruno P. Lima, and Bozena Zemaitaitis

Department of Microbiology and Immunology, Loyola University Medical School, 2160 S. First Ave., Bldg. 105, Maywood, Illinois 60153

Received 5 December 2007/ Accepted 10 January 2008

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 phosphotransacetylase (Pta)-acetate kinase (AckA) pathway, can activate the transcription of cpxP in a CpxA-independent manner by donating its phosphoryl group to CpxR. We tested this hypothesis by measuring the transcription of cpxP using mutants with mutations in the CpxAR pathway, mutants with mutations in the Pta-AckA pathway, and mutants with a combination of both types of mutations. From this epistasis analysis, we learned that CpxR integrates diverse stimuli. The stimuli 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 interactions between central metabolism and signal transduction can be quite complex and that successful investigations of such interactions must include a complete epistatic analysis.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Loyola University Medical School, 2160 S. First Ave., Bldg. 105, Maywood, IL 60153. Phone: (708) 216-5814. Fax: (708) 216-9574. E-mail: awolfe{at}lumc.edu

{triangledown} Published ahead of print on 25 January 2008.

Journal of Bacteriology, April 2008, p. 2314-2322, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01906-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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