Cpx signaling pathway monitors biogenesis and affects assembly and expression of P pili

P pili are important virulence factors in uropathogenic Escherichia cell. T he Cps two-component signal transduction system controls a stress response and is activated by misfolded proteins in the periplasm. We have discovered new functions for the Cpx pathway, indicating that it may play a critical role in pathogenesis. P pili are assembled via the chaperone/usher pathway. Subunits that go 'OFF-pathway' during pilus biogenesis generate a signal. This signal is derived from the misfolding and aggregation of subunits that failed to come into contact with the chaperone in the periplasm. In respon se, Cpx not only controls the stress response, but also controls genes nece ssary for pilus biogenesis, and is involved in regulating the phase variati on of pap expression and, potentially, the expression of a panoply of other virulence factors. This study demonstrates how the prototypic chaperone/us her pathway is intricately linked and dependent upon a signal system.