Pathogenic Significance of nrdD-like Gene in Virulent Porphyromonas gingivalis Strain

Objectives: Abscess-forming strains of P. gingivalis (AF-Pg) specifically possess an insertion sequence (IS1598). We had identified a common insertion site of IS1598 among AF-Pg in the promoter region of nrdD-like gene, which is homologous to nrdD encoding ribonucleotide reductase ofEscherichia coli . Furthermore, the mRNA expression ofnrdD -like gene was commonly enhanced in AF-Pg as compared to Pg strains lacking the abscess-forming ability. We hypothesized that the increased expression of the nrdD-like gene might be an important factor for the virulence of Pg. In the current study, we aimed to investigate the pathogenic significance of the nrdD-like gene for the virulence of Pg, especially for the abscess formation. Methods: The deficient mutant of the nrdD-like gene was constructed using the Pg W83 strain, which was known to be an AF-Pg. Inactivation of the gene was accomplished by homologous recombination of an erythromycin-resistance gene into the open reading frame. Abscess-forming ability, growth rate and sensitivity to hydrogen peroxide were examined and compared between the deficient mutant (d-W83) and the parent strain W83 (p-W83). Results: The d-W83 almost lost the ability to form necrotic abscess in mouse skin model, while the parent-W83 demonstrated the known ability. The growth rate of the d-W83 was also declined as compared to the p-W83 (doubling time: 6 hours for d-W83, 3 hours for p-W83). Further the d-W83 altered the sensitivity to hydrogen peroxide, demonstrating more growth depression comparing to the p-W83. Conclusion: The nrdD-like gene may have an important role for the growth of Pg and has an influence on the abscess-forming ability. Since ribonucleotide reductase is sensitive to O2, enhanced expression ofnrdD -like gene may be an advantage for the microorganisms under O2-stress environment, such as in the host.