The CpxRA Signal Transduction System of Escherichia coli : Growth-Related Autoactivation and Control of Unanticipated Target Operons

Abstract

In Escherichia coli, the CpxRA two-component signal transduction system senses and responds to aggregated and misfolded proteins in the bacterial envelope. We show that CpxR-P (the phosphorylated form of the cognate response regulator) activatescpxRA expression in conjunction with RpoS, suggesting an involvement of the Cpx system in stationary-phase survival. Engagement of the CpxRA system in functions beyond protein management is indicated by several putative targets identified after a genomic screening for the CpxR-P recognition consensus sequence. Direct negative control of the newly identified targets motABcheAW (specifying motility and chemotaxis) and tsr (encoding the serine chemoreceptor) by CpxR-P was shown by electrophoretic mobility shift analysis and Northern hybridization. The results suggest that the CpxRA system plays a core role in an extensive stress response network in which the coordination of protein turnover and energy conservation may be the unifying element.

The CpxRA two‐component system contributes to Legionella pneumophila virulence

“…kinase as well as a phosphatase of CpxR, where phosphorylated CpxR (CpxRP) is considered the active regulatory form (Raivio and Silhavy, 1997). Investigations to identify CpxRA regulon members in E. coli identified CpxRP as a direct activator of the cpxRA operon; a scenario presumed to occur in other Enterobacteriaceae due to the presence of a consensus CpxR binding site motif in the promoter region upstream of cpxRA (De Wulf et al, 1999, Raivio et al, 1999, De Wulf et al, 2000, Slamti and Waldor, 2009). Based on the results of this study, we favor a similar model of direct positive autoregulation to also occur in L. pneu-mophila Lp02 for the following reasons.…”

Just scratching the surface: an expanding view of the Cpx envelope stress response

“…Finally, cytoplasmic or growth signals can be integrated into the Cpx pathway downstream of CpxA, through CpxR. The expression of cpxRA is activated at the onset of stationary phase (De Wulf et al, 1999), and in E. coli strain MC4100, this growth-related activation is CpxRdependent but CpxA-independent (DiGiuseppe & Silhavy, 2003). CpxR can also be activated independently of CpxA when cells are grown in the presence of excess carbon, such as glucose or pyruvate (Wolfe et al, 2008).…”

“…Further repression of the csgBA operon is achieved indirectly through the CpxR-mediated inhibition of expression of the csgDEFG operon, which encodes the major transcriptional activator of curli expression, CsgD (Dorel et al, 1999;Prigent-Combaret et al, 2001;Jubelin et al, 2005;Ogasawara et al, 2010). Flagellar motility of E. coli K-12 is also decreased by the Cpx response (De Wulf et al, 1999). Regulation of motility appears to occur at several levels.…”

“…Regulation of motility appears to occur at several levels. CpxR directly represses expression of the motABcheAW, tsr and aer genes, encoding components of the flagellar motor and chemotaxis and aerotaxis proteins (De Wulf et al, 1999. Microarray results also suggest that expression of the flagellar master regulator FlhC An expanding view of the Cpx envelope stress response is downregulated in response to overexpression of NlpE (Price and Raivio, in preparation).…”

“…Downregulation of nonessential protein complexes may relieve the burden on the envelope protein folding machinery when misfolded proteins are already abundant (MacRitchie et al, 2008a). Alternatively or in addition, the repression of these energy-intensive structures may help to conserve finite cellular resources during times of stress (De Wulf et al, 1999). There is also a growing appreciation of the connection between the Cpx response and IM proteins.…”