Enhancement of t-PA-mediated plasminogen activation by bacterial surface receptors

Abstract

Summary A total of 63 strains representing 7 species of plasminogen binding bacteria, were examined for the ability to potentiate t-PA and urokinase (u-PA) mediated activation of human plasminogen to plasmin. Tested species included β-haemolytic streptococci groups A, C, and G, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Proteus mirabilis. The effect on plasminogen activation was measured using a coupled enzymatic assay with a chromogenic substrate. The changes in absorbance were found to be linear functions of t2 in agreement with theoretical expectations. Most plasminogen binding strains were capable to dramatically enhance the rate of t-PA induced plasminogen activation. The most pronounced potentiation was observed with a Streptococcus equisimilis strain which increased the activation rate 130-fold. High potentiations was also detected for N. meningitidis and S. pneumoniae strains. P. mirabilis was an exception as some strains were capable to bind plasminogen without any influence on plasminogen activation. Also, u-PA mediated plasminogen activation was enhanced in the presence of bacteria. However the stimulation factor obtained were in most strains much less than those obtained with t-PA. For different strains within a species, the capability to enhance the rate of the t-PA mediated activation correlated with plasminogen binding (r=0.74–0.92). Both plasminogen binding and the stimulation of plasminogen activation were abolished in the presence of 6-aminohexanoic acid (6-AHA, ɛ-aminocaproic acid) suggesting that the lysine-binding sites in the plasminogen molecule are involved in both phenomena. The binding of plasminogen and facilitation of its activation provide bacteria with an active proteolytic shield of possible importance in tissue penetration and infection.