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Absorption of kininogen from human plasma by Streptococcus pyogenes is followed by the release of bradykinin
A Ben Nasr1, H Herwald, U Sjöbring
1Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, P.O. Box 94, S-221 00 Lund, Sweden.
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.
Insights
Streptococcus pyogenes M-proteins bind high-molecular-mass kininogen (HK) from plasma. Bacterial M-proteins cleave HK, releasing bradykinin (BK), a vasoactive peptide, at the infection site.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- High-molecular-mass kininogen (HK) is the precursor to the vasoactive peptide bradykinin (BK).
- Streptococcus pyogenes utilizes M-proteins, crucial virulence factors, to interact with host factors.
- Previous studies indicated HK binding to S. pyogenes via M-proteins.
Purpose of the Study:
- To investigate the interaction between S. pyogenes M-proteins and HK.
- To determine if bacterial binding leads to HK cleavage and BK release.
- To elucidate the mechanism of BK generation at the site of S. pyogenes infection.
Main Methods:
- Incubation of M-protein-expressing S. pyogenes with human plasma.
- Analysis of HK absorption by bacteria.
- Characterization of HK degradation products on the bacterial surface.
- Assay for BK release upon addition of activated plasma prekallikrein.
Main Results:
- M-protein-expressing S. pyogenes effectively absorbed HK from human plasma.
- HK bound to bacteria exhibited cleavage patterns indicative of BK generation.
- Co-incubation with plasma prekallikrein significantly enhanced BK release from bacteria pre-incubated with plasma.
Conclusions:
- S. pyogenes M-proteins facilitate the capture and cleavage of HK, leading to BK release.
- This bacterial-mediated BK generation represents a novel mechanism influencing host-pathogen interactions.
- The release of BK at the infection site may modulate inflammation and host response during S. pyogenes infections.