Degradation of host heme proteins by lysine- and arginine-specific cysteine proteinases (gingipains) of Porphyromonas gingivalis.
Porphyromonas gingivalis can use hemoglobin bound to haptoglobin and heme complexed to hemopexin as heme sources; however, the mechanism by which hemin is released from these proteins has not been defined. In the present study, using a variety of analytical methods, we demonstrate that lysine-specific cysteine proteinase of P. gingivalis (gingipain K, Kgp) can efficiently cleave hemoglobin, hemopexin, haptoglobin, and transferrin. Degradation of hemopexin and transferrin in human serum by Kgp was also detected; however, we did not observe extensive degradation of hemoglobin in serum by Kgp. Likewise the beta-chain of haptoglobin was partially protected from degradation by Kgp in a haptoglobin-hemoglobin complex. Arginine-specific gingipains (gingipains R) were also found to degrade hemopexin and transferrin in serum; however, this was observed only at relatively high concentrations of these enzymes. Growth of P. gingivalis strain A7436 in a minimal media with normal human serum as a source of heme correlated not only with the ability of the organism to degrade hemoglobin, haptoglobin, hemopexin, and transferrin but also with an increase in gingipain K and gingipain R activity. The ability of gingipain K to cleave hemoglobin, haptoglobin, and hemopexin may provide P. gingivalis with a usable source of heme for growth and may contribute to the proliferation of P. gingivalis within periodontal pockets in which erythrocytes are abundant.
Sroka
A
A
Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Sztukowska
M
M
Potempa
J
J
Travis
J
J
Genco
C A
CA
D018829:Adhesins, Bacterial; D001798:Blood Proteins / Q000378:metabolism; D003470:Culture Media; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000302:isolation & purification / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism*; D006801:Humans; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000254:growth & development
D018829:Adhesins, Bacterial; D001798:Blood Proteins; D003470:Culture Media; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D006420:Hemeproteins; D003546:Cysteine Endopeptidases