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

Abstract

To detect and effectively respond to damage to the cell envelope, Gram‐negative bacteria possess multiple envelope stress responses. Among these, the CpxAR two‐component system has been shown to sense the presence of misfolded periplasmic proteins and increase the production of envelope‐localized protein folding and degrading factors in response. However, recent studies have revealed that additional parameters, such as adhesion and central metabolism, can also be sensed by the Cpx signalling system. The discovery that the Cpx regulon contains dozens to hundreds of genes indicates that the cellular functions of the Cpx response are also likely much broader than previously realized. These newly recognized functions include other aspects of envelope maintenance, communication with other regulatory pathways, and pathogenesis. A new model is emerging in which the Cpx response integrates diverse signals and promotes cell survival by protecting the envelope in multiple ways.

Expression of the Yersinia enterocolitica O:3 LPS O-antigen and outer core gene clusters is RfaH-dependent

“…This system responds to a broad range of stimuli related to perturbations in the bacterial cell envelope, including salts, metals, pH, lipids and misfolded proteins. The fact that both the YeO3-DrfaH and YeO3-c-R1 strains showed significant downregulation of the periplasmic repressor CpxP and higher levels of the CpxR protein indicated that bacteria respond to changes in cell wall integrity (Hunke et al, 2012;Vogt & Raivio, 2012). Overall, our data did not indicate massive alterations in the expression of membrane proteins, and transcriptomics and quantitative proteomics do not allow us to draw any conclusions about the state of the proteins.…”

PecS regulates the urate-responsive expression of type 1 fimbriae in Klebsiella pneumoniae CG43

“…The Cpx regulon contains approximately equal numbers of upregulated and downregulated genes, including those for pilus assembly, efflux pump biogenesis, adherence, antibiotic resistance, virulence and biofilm development (Vogt & Raivio, 2012). The deletion of cpxAR increased not only the expression of pecS and pecM (Fig.…”

High-resolution view of bacteriophage lambda gene expression by ribosome profiling

“…The set of genes involved in phosphate metabolism and transport responds to cellular phosphate limitation, which may occur in the induced cell; the involvement of pho genes in lambda growth has been noted (25). The genes cpxP, htpX, and degP are activated by the two component system encoded by cpxR/ A, which senses envelope stress (26), a plausible response to such phage proteins as the lysis set that are made at late times of induction. Finally, there is a set of up-regulated genes that mostly have known function, but no obvious relation to phage development; examples are shown in Fig.…”