| 1. |
- Herwald, Heiko, et al.
(author)
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Streptococcal cysteine proteinase releases kinins: a novel virulence mechanism
- 1996
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In: Journal of Experimental Medicine. - 1540-9538. ; 184:2, s. 665-673
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Journal article (peer-reviewed)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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| 2. |
- Kihlberg, B M, et al.
(author)
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Protein H, an antiphagocytic surface protein in Streptococcus pyogenes
- 1999
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In: Infection and Immunity. - 1098-5522. ; 67:4, s. 1708-1714
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Journal article (peer-reviewed)abstract
- Surface-associated M protein is a major virulence factor in Streptococcus pyogenes which confers bacterial resistance to phagocytosis. However, many S. pyogenes strains also express additional structurally related so-called M-like proteins. The strain studied here is of the clinically important M1 serotype and expresses two structurally related surface proteins, the M1 protein and protein H. Mutants were generated that expressed only one or none of these proteins at the bacterial surface. For survival in human blood either protein H or M1 protein was sufficient, whereas the double mutant was rapidly killed. The protein-binding properties of protein H, M1 protein, and the mutants suggest that bacterial binding of immunoglobulin G and factor H or factor H-like protein 1, which are regulatory proteins in the complement system, contribute to the antiphagocytic property.
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