Figure 2.

Examples of direct virulence gene regulation by the Cpx ESR. The Cpx response can be induced by various signals, with inputs entering at different points (surface attachment via NlpE to CpxA, external environmental changes via CpxA, and metabolic changes that alter the phosphorylation state of CpxR independently from CpxA). CpxP acts as a chaperone for misfolded proteins, directing them to destruction by the DegP protease (see text) and also negatively regulates the system, perhaps by interacting with CpxA. Phosphorylated CpxR activates the promoters of protein degradation factors (e.g., degP), protein-folding factors (e.g. dsbA) ands in multiple species, as well as many other genes associated with inner membrane functions. DegP and DsbA can reduce stress by promoting efficient assembly of the bundle forming pilus and Pap pilus in EPEC and UPEC, respectively. In addition, CpxR represses the promoters of the bfp and pap operons encoding these pili. In Y. pseudotuberculosis (Y. ptb) CpxR represses expression of several components of the Ysc-Yop T3SS. In Shigella sonnei CpxR directly activates the promoter of the gene encoding the major virulence regulator VirF, which leads to increased T3SS production because one VirF-induced target is the gene encoding the T3SS positive regulator NlpE/VirB (see text). CpxR also controls the T4SS in L. pneumophila by inducing genes encoding structural components (icm/dot) and by activating or repressing genes encoding some of the effectors exported by the T4SS.