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* Lund University, Department of Laboratory Medicine, Section of Medical Protein Chemistry, University Hospital Malmö, Malmö, Sweden;
Jagiellonian University, Department of Microbiology, Krakow, Poland;
University of Georgia, Department of Biochemistry and Molecular Biology, Athens, GA 30602; and
Lund University, Department of Laboratory Medicine, Section of Medical Microbiology, University Hospital Malmö, Malmö, Sweden
Periodontitis is an inflammatory disease of the supporting structures of the teeth and is caused by, among other agents, Porphyromonas gingivalis. P. gingivalis is very resistant to killing by human complement, which is present in a gingival fluid at 70% of the serum concentration. We found that the incubation of human serum with purified cysteine proteases of P. gingivalis (gingipains) or P. gingivalis wild-type strains W83 and W50 resulted in a drastic decrease of the bactericidal activity of the serum. In contrast, serum treated with P. gingivalis mutants lacking gingipains (particularly strains without HRgpA) maintained significant bactericidal activity. To understand in detail the mechanism by which gingipains destroy the serum bactericidal activity, we investigated the effects of gingipains on the human complement system. We found that all three proteases degraded multiple complement components, with arginine-specific gingipains (HRgpA and RgpB) being more efficient than lysine-specific gingipain (Kgp). Interestingly, all three proteases at certain concentrations were able to activate the C1 complex in serum, which resulted in the deposition of C1q on inert surfaces and on bacteria themselves. It is therefore plausible that P. gingivalis activates complement when present at low numbers, resulting in a local inflammatory reaction and providing the bacteria with a colonization opportunity and nutrients. At later stages of infection the concentration of proteases is high enough to destroy complement factors and thus render the bacteria resistant to the bactericidal activity of complement.
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1 This work was supported by the Swedish Foundation for Strategic Research (INGVAR), the Swedish Medical Research Council, the Foundations of Österlund, Kock, and Borgström, King Gustav V 80th Anniversary Foundation, research grants from the University Hospital in Malmö (to A.B.), and grants from the National Institutes of Health (DE 09761) and the Committee of Scientific Research (Poland) (KBN 3 PO4A 003 24; to J.P.). J.P. is a recipient of a Subsydium Profesorskie awarded by the Foundation for Polish Science (FNP; Warsaw, Poland).
2 Address correspondence and reprint requests to Dr. Anna M. Blom, Lund University; Department of Laboratory Medicine, Division of Medical Protein Chemistry University Hospital Malmö Entrance 46, The Wallenberg Laboratory, Floor 4, S-205 02 Malmö, Sweden. E-mail address: Anna.Blom{at}med.lu.se
3 Abbreviations used in this paper: MBL, mannose-binding lectin; GVB2+, gelatin barbiturate (veronal) buffer; DGVB2+, dextrose-GVB2+; LB, Luria-Bertani; NHS, normal human serum; pAb, polyclonal antibody.
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