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Journal of Bacteriology, August 1999, p. 4905-4913, Vol. 181, No. 16
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Hemoglobinase Activity of the Lysine Gingipain Protease (Kgp) of Porphyromonas gingivalis W83

Janina P. Lewis,1 Janet A. Dawson,1 James C. Hannis,2 David Muddiman,2 and Francis L. Macrina1,*

Institute of Oral and Craniofacial Molecular Biology1 and Department of Chemistry,2 Virginia Commonwealth University, Richmond, Virginia 23298

Received 8 March 1999/Accepted 2 June 1999

Porphyromonas gingivalis, an important periodontal disease pathogen, forms black-pigmented colonies on blood agar. Pigmentation is believed to result from accumulation of iron protoporphyrin IX (FePPIX) derived from erythrocytic hemoglobin. The Lys-X (Lys-gingipain) and Arg-X (Arg-gingipain) cysteine proteases of P. gingivalis bind and degrade erythrocytes. We have observed that mutations abolishing activity of the Lys-X-specific cysteine protease, Kgp, resulted in loss of black pigmentation of P. gingivalis W83. Because the hemagglutinating and hemolytic potentials of mutant strains were reduced but not eliminated, we hypothesized that this protease played a role in acquisition of FePPIX from hemoglobin. In contrast to Arg-gingipain, Lys-gingipain was not inhibited by hemin, suggesting that this protease played a role near the cell surface where high concentrations of hemin confer the black pigmentation. Human hemoglobin contains 11 Lys residues in the alpha  chain and 10 Lys residues in the beta  chain. In contrast, there are only three Arg residues in each of the alpha  and beta  chains. These observations are consistent with human hemoglobin being a preferred substrate for Lys-gingipain but not Arg-gingipain. The ability of the Lys-gingipain to cleave human hemoglobin at Lys residues was confirmed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry of hemoglobin fragments resulting from digestion with the purified protease. We were able to detect several of the predicted hemoglobin fragments rendered by digestion with purified Lys-gingipain. Thus, we postulate that the Lys-gingipain of P. gingivalis is a hemoglobinase which plays a role in heme and iron uptake by effecting the accumulation of FePPIX on the bacterial cell surface.

* Corresponding author. Mailing address: Institute of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University, Box 980566, Richmond, VA 23298-0566. Phone: (804) 828-0149. Fax: (804) 828-0150. E-mail: macrina{at}vcu.edu.

Journal of Bacteriology, August 1999, p. 4905-4913, Vol. 181, No. 16
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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