Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage.
Abstract Porphyromonas gingivalis, the major causative bacterium of periodontitis, contributes significantly to elevated proteolytic activity at periodontal pockets owing to the presence of both bacteria and host, predominantly neutrophil-derived, serine proteases. Normally the activity of the latter enzymes is tightly regulated by endogenous proteins, including elafin, a potent neutrophil elastase and proteinase 3 inhibitor released from epithelial cells at sites of inflammation. Here, we report that all three gingipains (HRgpA, RgpB, and Kgp) have the ability to degrade elafin, with RgpB being far more efficient than other gingipains. RgpB efficiently inactivates the inhibitory activity of elafin at subnanomolar concentrations through proteolysis limited to the Arg22-Cys23 peptide bond within the surface loop harboring the inhibitor active site. Notably, elafin resists inactivation by several Staphylococcus aureus-derived serine and cysteine proteases, confirming the high stability of this protein against proteolytic degradation. Therefore, we conclude that elafin inactivation by RgpB represents a specific pathogenic adaptation of P. gingivalis to disturb the protease-protease inhibitor balance in the infected gingival tissue. This contributes to enhanced degradation of host proteins and generation of a pool of peptides serving as nutrients for this asaccharolytic pathogen.
Kantyka
Tomasz
T
Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, D-24105 Kiel, Germany.
Latendorf
Ties
T
Wiedow
Oliver
O
Bartels
Joachim
J
Gläser
Regine
R
Dubin
Grzegorz
G
Schröder
Jens-Michael
JM
Potempa
Jan
J
Meyer-Hoffert
Ulf
U
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D057056:Cysteine Proteases / Q000378:metabolism; D053492:Elafin / Q000737:chemistry / Q000378:metabolism*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D020836:Protein Structure, Quaternary; D057057:Serine Proteases / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology; D013379:Substrate Specificity
D018829:Adhesins, Bacterial; D053492:Elafin; D000080867:Gingipain Cysteine Endopeptidases; D057056:Cysteine Proteases; D057057:Serine Proteases; D003546:Cysteine Endopeptidases