Identification of two laminin-binding fimbriae, the type 1 fimbria of Salmonella enterica serovar typhimurium and the G fimbria of Escherichia coli, as plasminogen receptors.

Escherichia coli strains carrying recombinant plasmids encoding either the type 1 fimbria of Salmonella enterica serovar Typhimurium or the G fimbria of E. coli exhibited binding of human 125I-Glu-plasminogen and enhanced the tissue-type plasminogen activator-catalyzed conversion of plasminogen to plasmin. Purified type 1 or G fimbriae similarly bound plasminogen and enhanced its activation. The binding of plasminogen did not involve the characteristic carbohydrate-binding property of the fimbriae but was inhibited at low concentrations by the lysine analog epsilon-aminocaproic acid. Because these fimbrial types bind to laminin of basement membranes (M. Kukkonen et al., Mol. Microbiol. 7:229-237, 1993; S. Saarela et al., Infect. Immun. 64:2857-2860, 1996), the results demonstrate a structural unity in the creation and targeting of bacterium-bound proteolytic plasmin activity to basement membranes.

Plasminogen receptors. Turning Salmonella and Escherichia coli into proteolytic organisms.

We evaluated in vitro the hypothesis that bacterial adhesiveness to the mammalian extracellular matrix and the activation of plasminogen on bacterial plasminogen receptors promote bacterial penetration through basement membranes. We used the strain SH401 of Salmonella enterica serovar Typhimurium, which adheres to the high-mannose chains of laminin, a major glycoprotein of basement membranes, and expresses plasminogen receptors. Bacterium-bound plasmin was able to degrade laminin and extracellular matrix preparations as well as to potentiate the penetration of bacteria through a reconstituted basement membrane. The results suggest that metastatic tumour cells and bacterial pathogens use similar mechanisms to penetrate through tissue barriers.