The periodontopathogen Porphyromonas gingivalis is an obligate anaerobe that is devoid of catalase but exhibits a relatively high degree of resistance to peroxide stress. In the present study, we demonstrate that P. gingivalis contains a Dps homologue that plays an important role in the protection of cells from peroxide stress. The Dps protein isolated from P. gingivalis displayed a ferritin-like spherical polymer consisting of 19-kDa subunits. Molecular cloning and sequencing of the gene encoding this protein revealed that it had a high similarity in nucleotide and amino acid sequences to Dps proteins from other species. The expression of Dps was significantly increased by exposure of P. gingivalis to atmospheric oxygen in an OxyR-dependent manner, indicating that it is regulated by the reactive oxygen species-regulating gene oxyR. The Dps-deficient mutants, including the dps single mutant and the ftn dps double mutant, showed no viability loss upon exposure to atmospheric oxygen for 6 h. In contrast to the wild type, however, these mutants exhibited the high susceptibility to hydrogen peroxide, thereby disrupting the viability. On the other hand, no significant difference in sensitivity to mitomycin C and metronidazole was observed between the wild type and the mutants. Furthermore, the dps single mutant, compared with the wild type, showed a lower viability in infected human umbilical vein endothelial cells.Atmospheric oxygen is metabolically converted to reactive oxygen species (ROS), including superoxide anion radical, hydrogen peroxide, hydroxy radical, and singlet oxygen, in bacterial cells. ROS are also generated by phagocytic host cells such as polymorphonuclear leukocytes and macrophages and attack invading bacterial cells. It is widely recognized that two cellular systems function to protect organisms from oxidative stresses (15,33). One is regulated by antioxidant enzymes in which molecular oxygen and ROS are diminished or eliminated (42). Superoxide dismutase (SOD), catalase, peroxidase, and oxidase are involved in this reaction. The other is catalyzed by endonucleases by which oxidatively damaged nucleic acids are repaired. This includes Escherichia coli exonuclease III and endonuclease IV (51). These two systems cooperatively function to minimize the detrimental effects of ROS upon cells, as evidenced by the presence of common regulatory genes such as oxyR (43).Porphyromonas gingivalis is a gram-negative obligate anaerobe belonging to the division Cytophagales (23). This bacterium is one of the organisms that is most strongly associated with chronic adult periodontitis and expresses numerous potential virulence factors, such as fimbriae, hemagglutinins, lipopolysaccharides, and various proteases that are capable of hydrolyzing collagen, immunoglobulins, iron-binding proteins, and complement factors (21, 27). P. gingivalis, by definition, cannot grow in aerobic conditions but exhibits a high degree of aerotolerance. This aerotolerance enables the organism to survive in periodontal pockets that are ...