Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection

PLoS Pathog. 2006 Jul;2(7):e76. doi: 10.1371/journal.ppat.0020076.


The efficient clearance of microbes by neutrophils requires the concerted action of reactive oxygen species and microbicidal components within leukocyte secretory granules. Rubrerythrin (Rbr) is a nonheme iron protein that protects many air-sensitive bacteria against oxidative stress. Using oxidative burst-knockout (NADPH oxidase-null) mice and an rbr gene knockout bacterial strain, we investigated the interplay between the phagocytic oxidative burst of the host and the oxidative stress response of the anaerobic periodontal pathogen Porphyromonas gingivalis. Rbr ensured the proliferation of P. gingivalis in mice that possessed a fully functional oxidative burst response, but not in NADPH oxidase-null mice. Furthermore, the in vivo protection afforded by Rbr was not associated with the oxidative burst responses of isolated neutrophils in vitro. Although the phagocyte-derived oxidative burst response was largely ineffective against P. gingivalis infection, the corresponding oxidative response to the Rbr-positive microbe contributed to host-induced pathology via potent mobilization and systemic activation of neutrophils. It appeared that Rbr also provided protection against reactive nitrogen species, thereby ensuring the survival of P. gingivalis in the infected host. The presence of the rbr gene in P. gingivalis also led to greater oral bone loss upon infection. Collectively, these results indicate that the host oxidative burst paradoxically enhances the survival of P. gingivalis by exacerbating local and systemic inflammation, thereby contributing to the morbidity and mortality associated with infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacteroidaceae Infections / genetics
  • Bacteroidaceae Infections / immunology*
  • Bacteroidaceae Infections / metabolism
  • Disease Models, Animal
  • Female
  • Ferredoxins / deficiency
  • Ferredoxins / genetics
  • Ferredoxins / immunology*
  • Hemerythrin
  • Humans
  • Immunity, Mucosal / genetics
  • Immunity, Mucosal / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidases / deficiency
  • NADPH Oxidases / genetics
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Oxidative Stress / genetics
  • Oxidative Stress / immunology*
  • Porphyromonas gingivalis / genetics
  • Porphyromonas gingivalis / immunology*
  • Porphyromonas gingivalis / metabolism
  • Respiratory Burst / genetics
  • Respiratory Burst / immunology*
  • Rubredoxins


  • Antioxidants
  • Bacterial Proteins
  • Ferredoxins
  • Hemerythrin
  • Rubredoxins
  • rubrerythrins
  • NADPH Oxidases