Binding of tissue-type plasminogen activator (t-PA) to Neisseria meningitidis and Haemophilus influenzae

Abstract

Forty-nine bacterial strains representing five species known to interact with human plasminogen were tested for the ability to bind the two major human plasminogen activators, t-PA and urokinase. The bacterial species tested included Haemophilus influenzae, Neisseria meningitidis, Streptococcus pyogenes, Streptococcus equisimilis and human group G streptococci. All N. meningitidis and 11 of 14 H. influenzae strains displayed substantial binding of t-PA with values in the range of 20-46%. On the contrary, none of the streptococcal strains bound significant amounts of tPA. With urokinase no binding could be found for any of the bacterial species tested. Scatchard analysis with a selected H. influenzae strain (HI23354) demonstrated 10,000 receptors per bacterium for t-PA with a Kd value of about 20 nmol l-1. The corresponding values with a selected N. meningitidis strain (Mo 52) was 8500 receptors per bacterium and 70 nmol l-1. t-PA binding could be reduced about 40% by the addition of 10 mmol l-1 of the lysine analogue epsilon-aminocaproic acd (EACA) whereas no inhibitory effect could be demonstrated with arginine. Addition of 2 mumol l-1 of plasminogen which is enough to occupy all bacterial sites for plasminogen did not interfere with the t-PA binding, suggesting that the receptors for t-PA and plasminogen are distinct. Using very high plasminogen concentrations however, t-PA binding could be reduced by about 50% possibly due to an interaction between t-PA and plasminogen in the fluid phase. Our results demonstrate the occurrence of a previously unknown type of bacterial receptor that is capable of specifically binding t-PA.

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

“…Meningococci have been shown to be capable of binding plasminogen on its surface, and specific receptors were recently characterized (58). One of the two major plasminogen activators, tissue-type plasminogen activator, has been reported to be specifically bound on the bacterial surface (59). Induction of the second plasminogen activator, uPA, in the infected cell by the bacterium could be an alternative mechanism for plasminogen activation.…”

Pneumococcal phosphoglycerate kinase interacts with plasminogen and its tissue activator

“…Figure S5A, available online at www.thrombosis-online.com). Binding of tPA has already been reported to some non-streptococcal species, whereas no streptococcal binding to tPA and no bacterial binding to uPA has been demonstrated so far (36). The 3D structures of kringle 2 domain of tPA (34) and angiostatin (kringle domains 1 to 3) (37) have been reported.…”