P-pilus
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P fimbriae (also known as pyelonephritis-associated pili) or P pili or Pap are chaperon-usher type (specifically of the π family) fimbrial appendages found on the surface of many '' Escherichia coli'' bacteria. The P fimbriae is considered to be one of the most important virulence factor in uropathogenic ''E. coli'' and plays an important role in upper urinary tract infections. P fimbriae mediate adherence to host cells, a key event in the pathogenesis of urinary tract infections.


Structure and expression

P fimbriae are large, linear structures projecting from the surface of the bacterial cell. With lengths of 1-2um, the pili can be larger than the diameter of the bacteria itself. The main body of the fimbriae is composed of approx. 1000 copies of the major fimbrial subunit protein PapA, forming a helical rod. The short fimbrial tip is made of the subunits PapK, PapE, PapF and the tip adhesin PapG, which mediates the binding. The fimbriae is assembled by a chaperone-usher system, and proteins required for the assembly are expressed by the Pap operon, which is located on pathogenicity islands. The genes of the Pap operon encode five structural proteins (PapA, PapK, PapE, PapF and PapG), four proteins involved in the transport and assembly (PapD, PapH, PapC, PapJ) and two proteins (PapB, PapI) regulating the operon expression.


Role during infection

Adherence to host uroepithelial cells is a crucial step during the infection that allows uropathogenic ''E.coli'' to colonize the urinary tract and prevents bacterial removal during micturition. The binding of the P fimbriae to epithelial cells is mediated by the tip adhesin PapG. Four different alleles of PapG have been described, which bind to different
glycolipid Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connec ...
structures on host cells. In humans, especially variant papGII and papGIII have shown to be clinically relevant. Variant PapGII binds preferentially to globoside (GbO4), found abundantly on human kidney epithelial cells. PapGII triggers a strong inflammatory response which leads to tissue damage. Most ''E. coli'' strains causing pyelonephritis, urinary-source
bacteremia Bloodstream infections (BSIs), which include bacteremias when the infections are bacterial and fungemias when the infections are fungal, are infections present in the blood. Blood is normally a sterile environment, so the detection of microb ...
and
urosepsis Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may i ...
produce P pili with PapGII. PapGIII binds to the Forssmann antigen (GbO5) as well as isoreceptors present in the urinary tract of humans. ''E. coli'' strains carrying the papGIII gene are associated with lower urinary tract infections (cystitis) and asymptomatic bacteriuria. PapGI adhesins bind preferentially to globotriaosylceramide (GbO3), while the isoreceptors of PapGIV are unknown. ''E. coli'' carrying genes for PapGI and PapGIV are rarely found in ''E. coli'' causing infections in humans.


References

{{reflist Bacteriology