Cpx signaling pathway monitors biogenesis and affects assembly and expression of P pili.
P pili are important virulence factors in uropathogenic Escherichia coli. The Cpx 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 response, Cpx not only controls the stress response, but also controls genes necessary for pilus biogenesis, and is involved in regulating the phase variation of pap expression and, potentially, the expression of a panoply of other virulence factors. This study demonstrates how the prototypic chaperone/usher pathway is intricately linked and dependent upon a signal transduction system.
Hung
D L
DL
Department of Molecular Microbiology, Box 8230, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, MO 63110, USA.
Raivio
T L
TL
Jones
C H
CH
Silhavy
T J
TJ
Hultgren
S J
SJ
D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000502:physiology* / Q000648:ultrastructure; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009876:Operon; D033903:Periplasmic Proteins; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*
C078802:AtpA protein, E coli; D001426:Bacterial Proteins; C491730:CpxP protein, E coli; C110674:CpxP protein, bacteria; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D033903:Periplasmic Proteins; D014157:Transcription Factors; C116245:atpD protein, E coli; D036781:Fimbriae Proteins; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C490475:CpxA protein, E coli; C092472:CpxA protein, bacteria; C061682:DegP protease; D012697:Serine Endopeptidases