CpxP, a Stress-Combative Member of the Cpx Regulon

Abstract

The CpxA/R two-component signal transduction system ofEscherichia coli can combat a variety of extracytoplasmic protein-mediated toxicities. The Cpx system performs this function, in part, by increasing the synthesis of the periplasmic protease, DegP. However, other factors are also employed by the Cpx system for this stress-combative function. In an effort to identify these remaining factors, we screened a collection of random lacZ operon fusions for those fusions whose transcription is regulated by CpxA/R. Through this approach, we have identified a new locus,cpxP, whose transcription is stimulated by activation of the Cpx pathway. cpxP specifies a periplasmic protein that can combat the lethal phenotype associated with the synthesis of a toxic envelope protein. In addition, we show that cpxPtranscription is strongly induced by alkaline pH in a CpxA-dependent manner and that cpxP and cpx mutant strains display hypersensitivity to growth in alkaline conditions.

Involvement of the Cpx signal transduction pathway of E. coli in biofilm formation

“…CpxR activates extracytoplasmic stress-induced genes such as degP, dsbA, rotA, cpxP, etc. [11,14,15]. Target gene activation depends on the phosphorylation degree of the CpxR protein regulated by the phosphatase kinase activities of CpxA [16].…”

Molecular and proteome analyses highlight the importance of the Cpx envelope stress system for acid stress and cell wall stability in Escherichia coli

“…CpxA possesses both kinase and phosphatase activity, and its autophosphorylation activity is inhibited by CpxP (Fleischer et al 2007). The Cpx-TCS is induced by various stimuli including misfolded proteins , alkaline pH (Danese and Silhavy 1998), salt (Raivio and Silhavy 1997), changes in lipid composition (Mileykovskaya and Dowhan 1997), or attachment to abiotic surfaces (Otto and Silhavy 2002). Importantly, the outer membrane lipoprotein NlpE (new lipoprotein E) is required to activate the Cpx-TCS in response to surface attachment (Otto and Silhavy 2002).…”

“…In contrast, CpxP inhibits the Cpx-TCS in a negative feedback loop (Raivio et al 1999). Thereby, the cpxP gene is the strongest induced CpxR target gene under envelope stress conditions and the strongest induced gene during the initial phase of biofilm formation (Danese and Silhavy 1998;Beloin et al 2004) However, direct inhibition of the Cpx response by CpxP is only monitored after overproduction of CpxP (Raivio et al 1999). Nevertheless, deletion of cpxP results in mild induction of the Cpx response, which can be fully induced by other stimuli (Raivio et al 1999).…”

“…Nevertheless, deletion of cpxP results in mild induction of the Cpx response, which can be fully induced by other stimuli (Raivio et al 1999). In addition to its inhibitory function, CpxP is important for the quality control of misfolded envelope proteins that go "OFF" pathway during biogenesis (Danese and Silhavy 1998;Hung et al 2001;Isaac et al 2005). It is established that the inhibitory and the quality control functions of CpxP are linked.…”

Two different mechanisms of ampicillin resistance operating in strains ofVibrio choleraeO1 independent of resistance genes

“…Furthermore, these findings suggest that a three-protein complex comprising the YceI-like protein (inner membrane protein), cpxP (periplasmic protein) and OmpU (outer membrane protein, porin) contributes to the survival of an organism such as a fimbriate strain of V. cholerae O1 under an oxidative stress environment, because the cpxP protein is the oxidative stress-combative protein (Danese & Silhavy, 1998). Expression of the cpxP protein in V. cholerae O1 strain led to the suppression of twitching motility.…”