Streptococcal surface proteins activate the contact system and control its antibacterial activity.
Group G streptococci (GGS) are important bacterial pathogens in humans. Here, we investigated the interactions between GGS and the contact system, a procoagulant and proinflammatory proteolytic cascade that, upon activation, also generates antibacterial peptides. Two surface proteins of GGS, protein FOG and protein G (PG), were found to bind contact system proteins. Experiments utilizing contact protein-deficient human plasma and isogenic GGS mutant strains lacking FOG or PG showed that FOG and PG both activate the procoagulant branch of the contact system. In contrast, only FOG induced cleavage of high molecular weight kininogen, generating the proinflammatory bradykinin peptide and additional high molecular weight kininogen fragments containing the antimicrobial peptide NAT-26. On the other hand, PG protected the bacteria against the antibacterial effect of NAT-26. These findings underline the significance of the contact system in innate immunity and demonstrate that GGS have evolved surface proteins to exploit and modulate its effects.
Division of Infection Medicine, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden. kristofer.wollein_waldetoft@med.lu.se
Kristofer
K
Wollein Waldetoft
Lisbeth
L
Svensson
Matthias
M
Mörgelin
Anders I
AI
Olin
D Patric
DP
Nitsche-Schmitz
Lars
L
Björck
Inga-Maria
IM
Frick
D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D001770:Blood Bactericidal Activity / Q000276:immunology*; D001920:Bradykinin / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D019679:Kininogen, High-Molecular-Weight / Q000276:immunology / Q000378:metabolism; D013291:Streptococcus / Q000276:immunology* / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D019679:Kininogen, High-Molecular-Weight; D001920:Bradykinin