Arginine-specific cysteine proteinase (Arg-gingipain; formerly, argingipain) is one of the major extracellular proteinases produced by the oral anaerobic bacterium Porphyromonas gingivalis. To determine whether Arg-gingipain is important for periodontopathogenicity of the organism, Arg-gingipain-deficient mutants were constructed via gene disruption by use of suicide plasmid systems. First, Southern hybridization analyses suggested that two separate Arg-gingipain-encoding genes designated rgpA and rgpB existed on 12.5- and 7.8-kilobase pair HindIII chromosomal fragments of P. gingivalis ATCC33277, respectively. rgpA and rgpB single mutants were constructed by mobilization of a suicide plasmid. Then, an rgpA rgpB double mutant was isolated by electroporation with a second suicide plasmid. No proteolytic activity for Arg-gingipain was observed in either the cell extract or the culture supernatant of the rgpA rgpB mutant. The chemiluminescence response of polymorphonuclear leukocytes, which is closely related to their bactericidal function, was not inhibited by the culture supernatant of the rgpA rgpB mutant, while the wild type parent showed a significant inhibition of the response. The result suggests that Arg-gingipain is responsible for disruption of the function of polymorphonuclear leukocytes. In addition, the rgpA rgpB double mutations caused a marked decrease in the hemagglutination of P. gingivalis, indicating that a major part of the hemagglutinin activity of the organism is associated with the two genes. These findings demonstrate that Arg-gingipain makes a significant contribution to the virulence of P. gingivalis.

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				M. Tokuda, W. Chen, T. Karunakaran, and H. K. Kuramitsu Regulation of Protease Expression in Porphyromonas gingivalis Infect. Immun., November 1, 1998; 66(11): 5232 - 5237. [Abstract] [Full Text] [PDF]

				T. Kadowaki, K. Nakayama, F. Yoshimura, K. Okamoto, N. Abe, and K. Yamamoto Arg-gingipain Acts as a Major Processing Enzyme for Various Cell Surface Proteins in Porphyromonas gingivalis J. Biol. Chem., October 30, 1998; 273(44): 29072 - 29076. [Abstract] [Full Text] [PDF]

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				C. A. Genco, B. M. Odusanya, J. Potempa, J. Mikolajczyk-Pawlinska, and J. Travis A Peptide Domain on Gingipain R Which Confers Immunity against Porphyromonas gingivalis Infection in Mice Infect. Immun., September 1, 1998; 66(9): 4108 - 4114. [Abstract] [Full Text] [PDF]

				J. Potempa, J. Mikolajczyk-Pawlinska, D. Brassell, D. Nelson, I. B. Thogersen, J. J. Enghild, and J. Travis Comparative Properties of Two Cysteine Proteinases (Gingipains R), the Products of Two Related but Individual Genes of Porphyromonas gingivalis J. Biol. Chem., August 21, 1998; 273(34): 21648 - 21657. [Abstract] [Full Text] [PDF]

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				J. P. Lewis and F. L. Macrina IS195, an Insertion Sequence-Like Element Associated with Protease Genes in Porphyromonas gingivalis Infect. Immun., July 1, 1998; 66(7): 3035 - 3042. [Abstract] [Full Text] [PDF]

				J. Aduse-Opoku, M. Rangarajan, K. A. Young, and M. A. Curtis Maturation of the Arginine-Specific Proteases of Porphyromonas gingivalis W50 Is Dependent on a Functional prR2 Protease Gene Infect. Immun., April 1, 1998; 66(4): 1594 - 1600. [Abstract] [Full Text] [PDF]

				M. Tokuda, T. Karunakaran, M. Duncan, N. Hamada, and H. Kuramitsu Role of Arg-Gingipain A in Virulence of Porphyromonas gingivalis Infect. Immun., March 1, 1998; 66(3): 1159 - 1166. [Abstract] [Full Text] [PDF]

				T. Imamura, A. Banbula, P. J. B. Pereira, J. Travis, and J. Potempa Activation of Human Prothrombin by Arginine-specific Cysteine Proteinases (Gingipains R) from Porphyromonas gingivalis* J. Biol. Chem., May 25, 2001; 276(22): 18984 - 18991. [Abstract] [Full Text] [PDF]