| 1. |
- Ben Nasr, Abdelhakim, et al.
(författare)
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Absorption of kininogen from human plasma by Streptococcus pyogenes is followed by the release of bradykinin
- 1997
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Ingår i: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 326:3, s. 657-660
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Tidskriftsartikel (refereegranskat)abstract
- H-kininogen (high-molecular-mass kininogen, HK) is the precursor of the vasoactive peptide hormone bradykinin (BK). Previous work has demonstrated that HK binds to Streptococcus pyogenes through M-proteins, fibrous surface proteins and important virulence factors of these bacteria. Here we find that M-protein-expressing bacteria absorb HK from human plasma. The HK bound to the bacteria was found to be cleaved, and analysis of the degradation pattern suggested that the cleavage of HK at the bacterial surface is associated with the release of BK. Moreover, addition of activated plasma prekallikrein to bacteria preincubated with human plasma, resulted in BK release. This mechanism, by which a potent vasoactive and proinflammatory peptide is generated at the site of infection, should influence the host-parasite relationship during S. pyogenes infections.
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| 2. |
- Ben Nasr, Abdelhakim, et al.
(författare)
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Human kininogens interact with M protein, a bacterial surface protein and virulence determinant.
- 1995
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Ingår i: Biochemical Journal. - 0264-6021. ; 305:1, s. 80-173
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes, the most significant streptococcal species in clinical medicine, expresses surface proteins with affinity for several human plasma proteins. Here we report that kininogens, the precursors to the vasoactive kinins, bind to the surface of S. pyogenes. M protein, a surface molecule and a major virulence factor-in these bacteria, occurs in > 80 different serotypes. Among 49 strains of S. pyogenes, all of different M serotypes, 41 bound radiolabelled kininogens, whereas 6 M protein-negative mutant strains showed no affinity. M protein of most serotypes bind fibrinogen, and among the 55 strains tested, binding of kininogens was closely correlated to fibrinogen binding (r = 0.88, P < 0.0001). Western blotting, slot binding and enzyme immunoassay experiments demonstrated that M proteins isolated from S. pyogenes of three different M protein serotypes (M1, M6 and M46) bound kininogens. The affinity between kininogens and M1 protein was determined to be 5 x 10(7) M-1 and < or = 10(6) M-1 for high molecular weight (H-kininogen) and low molecular weight kininogen, respectively. The kininogen binding site was tentatively mapped to the N-terminal portion of M1 protein, and this site does not overlap the specific and separate binding sites for albumin, IgG and fibrinogen using monoclonal antibodies to, and synthetic peptides of, the kininogen sequence, the major M protein-binding site(s) was mapped to the C-terminal portion of the H-kininogen light chain. We anticipate that the kininogen-M protein interaction contributes to the host-parasite relationship in S. pyogenes infections.
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| 3. |
- Herwald, Heiko, et al.
(författare)
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Activation of the contact-phase system on bacterial surfaces - A clue to serious comlications in infections deseases
- 1998
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 4:3, s. 298-302
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Tidskriftsartikel (refereegranskat)abstract
- Fever, hypotension and bleeding disorders are common symptoms of sepsis and septic shock. The activation of the contact-phase system is thought to contribute to the development of these severe disease states by triggering proinflammatory and procoagulatory cascades; however, the underlying molecular mechanisms are obscure. Here we report that the components of the contact-phase system are assembled on the surface of Escherichia coil and Salmonella through their specific interactions with fibrous bacterial surface proteins, curli and fimbriae. As a consequence, the proinflammatory pathway is activated through the release of bradykinin, a potent inducer of fever, pain and hypotension. Absorption of contact-phase proteins and fibrinogen by bacterial surface proteins depletes relevant coagulation factors and causes a hypocoagulatory state. Thus, the complex interplay of microbe surface proteins and host contact-phase factors may contribute to the symptoms of sepsis and septic shock.
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| 4. |
- Herwald, Heiko, et al.
(författare)
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Streptococcal cysteine proteinase releases kinins: a novel virulence mechanism
- 1996
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Ingår i: Journal of Experimental Medicine. - 1540-9538. ; 184:2, s. 665-673
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Tidskriftsartikel (refereegranskat)abstract
- Previous work has indicated a crucial role for the extracellular cysteine proteinase of Streptococcus pyogenes in the pathogenicity and virulence of this important human pathogen. Here we find that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and from kininogens present in the human plasma, ex vivo. Kinin liberation in the plasma is due to the direct action of the streptococcal proteinase on the kininogens, and does not involve the previous activation of plasma prekallikrein, the physiological plasma kininogenase. Judged from the amount of released plasma kinins the bacterial proteinase is highly efficient in its action. This is also the case in vivo. Injection of the purified cysteine proteinase into the peritoneal cavity of mice resulted in a progressive cleavage of plasma kininogens and the concomitant release of kinins over a period of 5 h. No kininogen degradation was seen in mice when the cysteine proteinase was inactivated by the specific inhibitor, Z-Leu-Val-Gly-CHN2, before administration. Intraperitoneal administration into mice of living S. pyogenes bacteria producing the cysteine proteinase induced a rapid breakdown of endogenous plasma kininogens and release of kinins. Kinins are hypotensive, they increase vascular permeability, contract smooth muscle, and induce fever and pain. The release of kinins by the cysteine proteinase of S. pyogenes could therefore represent an important and previously unknown virulence mechanism in S. pyogenes infections.
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