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

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.