These possibilities

remain to be investigated. One model system that shows promise in revealing the role of the Cpx response in bacterium–host interactions involves the organism Xenorhabdus nematophila. X. nematophila associates mutualistically with the entomopathogenic nematode Steinernema carpocapsae; the bacterium IWR1 and the nematode cooperatively kill a variety of insect hosts (Chaston & Goodrich-Blair, 2010). Interestingly, inactivation of the Cpx response reduces the ability of X. nematophila to both colonize its nematode host and successfully infect an insect host (Herbert et al., 2007). Subsequent studies determined that the nematode colonization defect of the cpxR mutant likely results from diminished expression of the envelope-localized colonization factors NilA, NilB and NilC (Herbert Tran et al., 2009), while the virulence find more defect could be the result of insufficient expression of the

virulence-related transcriptional regulator LrhA (Herbert Tran & Goodrich-Blair, 2009). It therefore appears that the Cpx response has important functions in multiple stages of the X. nematophila life cycle. Further studies in this pathogen and others will undoubtedly improve our understanding of the role of the

Cpx response in bacterium–host interactions. It is now clear that the Cpx envelope stress response represents more than simply a means to detect and repair misfolded periplasmic proteins. A variety of signals can enter the Cpx signalling pathway at multiple points, with NlpE sensing adhesion, CpxA possibly sensing misfolded envelope proteins, and CpxR sensing growth and metabolism. A variety of target genes are regulated by phosphorylated CpxR, including those encoding envelope Transmembrane Transporters modulator protein complexes, IM proteins, peptidoglycan metabolic enzymes and other regulators. Finally, the Cpx response regulates virulence processes in numerous pathogens (Table 1). Most of these inducing cues and regulatory targets still pertain to the cell envelope, validating the original characterization of CpxAR as an envelope stress response; however, the Cpx response also promotes envelope function in diverse ways not previously recognized (summarized in Fig. 1). In spite of these advances, many questions remain.