Acquisition of plasmin activity by Fusobacterium nucleatum subsp nucleatumand potential contribution to tissue destruction during periodontitis

Fusobacterium nucleatum subsp. nucleatum has been associated with a variety of oral and nonoral infections such as periodontitis, pericarditis, bone i nfections, and brain abscesses. Several studies have shown the role of plas min, a plasma serine protease, in increasing the invasive capacity of micro organisms, In this study, we investigated the binding of human plasminogen to F. nucleatum subsp. nucleatum, and its subsequent activation into plasmi n, Plasminogen-binding activity of bacterial cells was demonstrated by a so lid-phase dot blot assay using an anti-plasminogen antibody. The binding ac tivity was heat resistant and involved cell-surface lysine residues since i t was abolished in the presence of the lysine analog e-aminocaproic acid, A ctivation of plasminogen coated bacteria occurred following incubation with either streptokinase, urokinase-type plasminogen activator (u-PA), or a Po rphyromonas gingivalis culture supernatant. In the case of the P. gingivali s culture supernatant, a cysteine protease was likely involved in the activ ation. The plasmin activity generated on the cell surface of F. nucleatum s ubsp, nucleatum could be inhibited by aprotinin. Activation of plasminogen by u-PA was greatly enhanced when plasminogen was bound to bacteria rather than in a free soluble form. u-PA-activated plasminogen-coated F. nucleatum subsp, nucleatum was found to degrade fibronectin, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Tissue inhibitor of me talloproteinase-l was also degraded by the plasmin activity generated on th e bacterial cells, This study suggests a possible role for plasminogen, whi ch is present in affected periodontal sites, in promoting tissue destructio n and invasion by nonproteolytic bacteria such as F. nucleatum subsp, nucle atum.