The conversion of fibrinogen to fibrin at the surface of curliated Escherichia coli bacteria leads to the generation of proinflammatory fibrinopeptides.
The inflammatory response to bacterial infection is the result of a complex interplay between bacterial products and host effector systems, such as the immune and complement systems. Here we show that Escherichia coli bacteria expressing fibrous surface proteins, known as curli, assemble and activate factors of the human coagulation cascade at their surface. As a result of this interaction, fibrinogen is converted to fibrin and fibrinogen-derived peptides, termed fibrinopeptides, are generated. The molecular mechanisms behind the bacteria-induced formation of fibrinopeptides were investigated and shown to be triggered by the activation of the contact system, also known as the kallikrein/kinin system or the intrinsic pathway of coagulation. Samples containing fibrinopeptides generated by the interaction between bacteria and plasma were injected into animals and the inflammatory response was monitored. We found that this treatment provoked an infiltration of white blood cells, and the induction of the proinflammatory cytokine MCP-1 at the inflamed site. Our results therefore demonstrate that activation of the coagulation system at the bacterial surface contributes to the pathophysiology of bacterial infectious diseases.
Persson
Kristin
K
Department of Cell and Molecular Biology, Lund University, S-221 84 Lund, Sweden.
Russell
Wayne
W
Mörgelin
Matthias
M
Herwald
Heiko
H
D000595:Amino Acid Sequence; D000818:Animals; D004926:Escherichia coli / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*
D018836:Inflammation Mediators; D010455:Peptides; D005337:Fibrin; D005340:Fibrinogen