The CpxAR Two-component System Regulates a Complex Envelope Stress Response in Gram Negative Bacteria
Stefanie Vogt, Nicole Acosta, Julia Wong, Junshu Wang and Tracy Raivio
from: Two-Component Systems in Bacteria (Edited by: Roy Gross and Dagmar Beier). Caister Academic Press, U.K. (2012)
The CpxA membrane bound sensor kinase utilizes a periplasmic sensing domain to detect a wide variety of stresses to the bacterial envelope. This information is communicated via typical two-component phosphotransfer mediated reactions to the response regulator CpxR. Phosphorylated CpxR binds upstream of numerous promoters to mediate adaptation. Initial studies of CpxA inducing signals and CpxR regulated genes demonstrated a role for this two-component system in responding to protein misfolding in the envelope. In this chapter, we discuss recent progress regarding the mechanisms of signal detection, transduction, and gene regulation employed by CpxA and CpxR. The data indicate that the majority of inducing cues are sensed through the periplasmic domain of CpxA and lead to the relief of one or more inhibitory controls that function to maintain Cpx pathway activity at low basal levels in the absence of envelope stress. Some activating signals also enter the pathway downstream of CpxA, in the cytoplasm. Analysis of the Cpx regulon in multiple organisms indicates that, in addition to regulating the production of well studied envelope protein folding and degrading factors, CpxA and CpxR also control the expression of cellular functions linked to cell wall modification, transport, translation, and regulation, indicating that adaptation to envelope stress involves broad changes in cellular physiology. The Cpx two-component system has been shown to impact virulence in a number of pathogens, and our current knowledge of this field is discussed read more ...