Kgp and RgpB, but Not RgpA, Are Important for Porphyromonas Gingivalis Virulence in the Murine Periodontitis Model

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2007 Jan 16

PMID 17220315

Citations 45

Authors

Rishi D Pathirana

Neil M OBrien-Simpson

Gail C Brammar

Nada Slakeski

Eric C Reynolds

Affiliations

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Abstract

The contributions of three proteinase genes (rgpA, rgpB, and kgp) to the virulence of Porphyromonas gingivalis W50 were investigated in the murine periodontitis model. Mice were orally inoculated with eight doses (1 x 10(10) cells per dose) of rgpA, rgpB, kgp, rgpA rgpB, or rgpA rgpB kgp isogenic mutants, and the level of alveolar bone loss, immune response induced, and number of bacterial cells per half maxilla were compared with those of animals inoculated with wild-type P. gingivalis. The kgp, rgpB, rgpA rgpB, and rgpA rgpB kgp isogenic mutants induced significantly (P < 0.05) less bone loss than the rgpA isogenic mutant and the wild type did, and the virulence of the rgpA isogenic mutant and the wild type were not significantly different. Mice inoculated with the wild type or the rgpA isogenic mutant exhibited significantly (P < 0.01) more P. gingivalis cells per half maxilla than mice inoculated with rgpB, kgp, rgpA rgpB, and rgpA rgpB kgp isogenic mutants or nonchallenged mice did, as determined using real-time PCR. A significant positive correlation was found between the number of P. gingivalis cells detected per half maxilla and the amount of alveolar bone loss induced. Enzyme-linked immunosorbent assay results showed that each isogenic mutant and the wild type induced a predominant P. gingivalis antigen-specific immunoglobulin G3 (IgG3) response. Furthermore, the kgp and rgpA rgpB kgp isogenic mutants induced significantly (P < 0.05) lower IgG3 antibody responses than the responses induced by the wild type or the rgpA, rgpB, and rgpA rgpB isogenic mutants. The results suggest that the order in which the proteinases contribute to the virulence of P. gingivalis in the murine periodontitis model is Kgp > or = RgpB >> RgpA.

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References

Marsh P, McDermid A, McKee A, Baskerville A . The effect of growth rate and haemin on the virulence and proteolytic activity of Porphyromonas gingivalis W50. Microbiology (Reading). 1994; 140 ( Pt 4):861-5. DOI: 10.1099/00221287-140-4-861. View

Evans R, Klausen B, Ramamurthy N, Golub L, Sfintescu C, Genco R . Periodontopathic potential of two strains of Porphyromonas gingivalis in gnotobiotic rats. Arch Oral Biol. 1992; 37(10):813-9. DOI: 10.1016/0003-9969(92)90115-o. View

Pavloff N, Potempa J, Pike R, Prochazka V, Kiefer M, Travis J . Molecular cloning and structural characterization of the Arg-gingipain proteinase of Porphyromonas gingivalis. Biosynthesis as a proteinase-adhesin polyprotein. J Biol Chem. 1995; 270(3):1007-10. DOI: 10.1074/jbc.270.3.1007. View

Baker P, Evans R, Roopenian D . Oral infection with Porphyromonas gingivalis and induced alveolar bone loss in immunocompetent and severe combined immunodeficient mice. Arch Oral Biol. 1994; 39(12):1035-40. DOI: 10.1016/0003-9969(94)90055-8. View

Kesavalu L, Holt S, Ebersole J . Trypsin-like protease activity of Porphyromonas gingivalis as a potential virulence factor in a murine lesion model. Microb Pathog. 1996; 20(1):1-10. DOI: 10.1006/mpat.1996.0001. View

Slakeski N, Cleal S, Reynolds E . Characterization of a Porphyromonas gingivalis gene prtR that encodes an arginine-specific thiol proteinase and multiple adhesins. Biochem Biophys Res Commun. 1996; 224(3):605-10. DOI: 10.1006/bbrc.1996.1073. View

Ebersole J, Kesavalu L, Schneider S, Machen R, Holt S . Comparative virulence of periodontopathogens in a mouse abscess model. Oral Dis. 1995; 1(3):115-28. DOI: 10.1111/j.1601-0825.1995.tb00174.x. View

Socransky S, Haffajee A, Cugini M, Smith C, Kent Jr R . Microbial complexes in subgingival plaque. J Clin Periodontol. 1998; 25(2):134-44. DOI: 10.1111/j.1600-051x.1998.tb02419.x. View

Slakeski N, Bhogal P, OBrien-Simpson N, Reynolds E . Characterization of a second cell-associated Arg-specific cysteine proteinase of Porphyromonas gingivalis and identification of an adhesin-binding motif involved in association of the prtR and prtK proteinases and adhesins into large complexes. Microbiology (Reading). 1998; 144 ( Pt 6):1583-1892. DOI: 10.1099/00221287-144-6-1583. View

10.

OLIVER R, Brown L . Periodontal diseases and tooth loss. Periodontol 2000. 1993; 2:117-27. DOI: 10.1111/j.1600-0757.1993.tb00224.x. View

11.

Okamoto K, Nakayama K, Kadowaki T, Abe N, Ratnayake D, Yamamoto K . Involvement of a lysine-specific cysteine proteinase in hemoglobin adsorption and heme accumulation by Porphyromonas gingivalis. J Biol Chem. 1998; 273(33):21225-31. DOI: 10.1074/jbc.273.33.21225. View

12.

Lamont R, Jenkinson H . Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev. 1998; 62(4):1244-63. PMC: 98945. DOI: 10.1128/MMBR.62.4.1244-1263.1998. View

13.

Genco C, Van Dyke T, Amar S . Animal models for Porphyromonas gingivalis-mediated periodontal disease. Trends Microbiol. 1998; 6(11):444-9. DOI: 10.1016/s0966-842x(98)01363-8. View

14.

Slakeski N, Cleal S, Bhogal P, Reynolds E . Characterization of a Porphyromonas gingivalis gene prtK that encodes a lysine-specific cysteine proteinase and three sequence-related adhesins. Oral Microbiol Immunol. 1999; 14(2):92-7. DOI: 10.1034/j.1399-302x.1999.140203.x. View

15.

Lewis J, Dawson J, Hannis J, Muddiman D, Macrina F . Hemoglobinase activity of the lysine gingipain protease (Kgp) of Porphyromonas gingivalis W83. J Bacteriol. 1999; 181(16):4905-13. PMC: 93978. DOI: 10.1128/JB.181.16.4905-4913.1999. View

16.

Bosshardt D, Lang N . The junctional epithelium: from health to disease. J Dent Res. 2004; 84(1):9-20. DOI: 10.1177/154405910508400102. View

17.

Persson G . Immune responses and vaccination against periodontal infections. J Clin Periodontol. 2005; 32 Suppl 6:39-53. DOI: 10.1111/j.1600-051X.2005.00800.x. View

18.

OBrien-Simpson N, Pathirana R, Paolini R, Chen Y, Veith P, Tam V . An immune response directed to proteinase and adhesin functional epitopes protects against Porphyromonas gingivalis-induced periodontal bone loss. J Immunol. 2005; 175(6):3980-9. DOI: 10.4049/jimmunol.175.6.3980. View

19.

Nonnenmacher C, Dalpke A, Rochon J, Flores-de-Jacoby L, Mutters R, Heeg K . Real-time polymerase chain reaction for detection and quantification of bacteria in periodontal patients. J Periodontol. 2005; 76(9):1542-9. DOI: 10.1902/jop.2005.76.9.1542. View

20.

Pathirana R, OBrien-Simpson N, Veith P, Riley P, Reynolds E . Characterization of proteinase-adhesin complexes of Porphyromonas gingivalis. Microbiology (Reading). 2006; 152(Pt 8):2381-2394. DOI: 10.1099/mic.0.28787-0. View