| 1. |
- Olsén, Arne, et al.
(författare)
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Identification of two protein-binding and functional regions of curli, a surface organelle and virulence determinant of Escherichia coli
- 2002
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:37, s. 34568-34572
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Tidskriftsartikel (refereegranskat)abstract
- Curli are surface organelles of Escherichia coli. These fibrous proteins, formed by polymerization of a 15-kDa subunit, are expressed by E. coli strains associated with severe infections in humans. A remarkable property of curli is their ability to interact with a wide range of human proteins, interactions that contribute to the enhanced virulence of curli-expressing E. coli. To define the protein-binding region(s) of curli, we investigated the binding properties of overlapping synthetic peptides covering the curli subunit. Two peptides, one covering a 24-amino acid residue sequence in the NH2-terminal half of the subunit (NNS24) and one corresponding to the 26 COOH-terminal residues (VDQ26), were found to bind a number of human proteins. Physiochemical analysis revealed that NNS24 adopts a thermally stable beta-structure, and in solution the peptide forms soluble multimers, predominantly octamers. Intact curli are known to activate the proinflammatory and procoagulant contact system, and when added to human plasma, the NNS24 and VDQ26 peptides induced the release of the potent vasoactive peptide bradykinin. The results map important curli functions to the regions corresponding to the NNS24 and VDQ26 sequences.
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| 2. |
- Persson, Kristin, et al.
(författare)
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Severe lung lesions caused by Salmonella are prevented by inhibition of the contact system
- 2000
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 192:10, s. 1415-1424
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Tidskriftsartikel (refereegranskat)abstract
- Vascular damage induced by trauma, inflammation, or infection results in an alteration of the endothelium from a nonactivated to a procoagulant, vasoconstrictive, and proinflammatory state, and can lead to life-threatening complications. Here we report that activation of the contact system by Salmonella leads to massive infiltration of red blood cells and fibrin deposition in the lungs of infected rats. These pulmonary lesions were prevented when the infected animals were treated with H-D-Pro-Phe-Arg-chloromethylketone, an inhibitor of coagulation factor XII and plasma kallikrein, suggesting that inhibition of contact system activation could be used therapeutically in severe infectious disease.
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| 3. |
- Persson, Kristin, et al.
(författare)
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The conversion of fibrinogen to fibrin at the surface of curliated E. coli bacteria leads to the generation of proinflammatory fibrinopeptides.
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:34, s. 31884-31890
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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