Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by Helicobacter pylori

Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19998-20003. doi: 10.1073/pnas.0906753106. Epub 2009 Nov 6.


Modification of eukaryotic proteins is a powerful strategy used by pathogenic bacteria to modulate host cells during infection. Previously, we demonstrated that Helicobacter pylori modify an unidentified protein within mammalian cell lysates in a manner consistent with the action of a bacterial ADP-ribosylating toxin. Here, we identified the modified eukaryotic factor as the abundant nuclear factor poly(ADP-ribose) polymerase-1 (PARP-1), which is important in the pathologies of several disease states typically associated with chronic H. pylori infection. However, rather than being ADP-ribosylated by an H. pylori toxin, the intrinsic poly(ADP-ribosyl) polymerase activity of PARP-1 is activated by a heat- and protease-sensitive H. pylori factor, resulting in automodification of PARP-1 with polymers of poly(ADP-ribose) (PAR). Moreover, during infection of gastric epithelial cells, H. pylori induce intracellular PAR-production by a PARP-1-dependent mechanism. Activation of PARP-1 by a pathogenic bacterium represents a previously unrecognized strategy for modulating host cell signaling during infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Animals
  • Catalytic Domain
  • Enzyme Activation
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Gastric Mucosa / cytology
  • HeLa Cells
  • Helicobacter Infections / metabolism
  • Helicobacter pylori / metabolism*
  • Humans
  • Mice
  • Mice, Knockout
  • Phosphorus Radioisotopes / metabolism
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*


  • Phosphorus Radioisotopes
  • Adenosine Diphosphate Ribose
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases