Antibacterial activity of the contact and complement systems is blocked by SIC, a protein secreted by Streptococcus pyogenes.
Recent studies have shown that activation of complement and contact systems results in the generation of antibacterial peptides. Streptococcus pyogenes, a major bacterial pathogen in humans, exists in >100 different serotypes due to sequence variation in the surface-associated M protein. Cases of invasive and life-threatening S. pyogenes infections are commonly associated with isolates of the M1 serotype, and in contrast to the large majority of M serotypes, M1 isolates all secrete the SIC protein. Here, we show that SIC interferes with the activation of the contact system and blocks the activity of antibacterial peptides generated through complement and contact activation. This effect promotes the growth of S. pyogenes in human plasma, and in a mouse model of S. pyogenes sepsis, SIC enhances bacterial dissemination, results which help explain the high frequency of severe S. pyogenes infections caused by isolates of the M1 serotype.
Division of Infection Medicine, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden. Inga-Maria.Frick@med.lu.se
Inga-Maria
IM
Frick
Oonagh
O
Shannon
Per
P
Åkesson
Matthias
M
Mörgelin
Mattias
M
Collin
Artur
A
Schmidtchen
Lars
L
Björck
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D016470:Bacteremia / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D003167:Complement Activation / Q000502:physiology*; D015926:Complement C3a / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; C097739:SIC protein, Streptococcus; D015926:Complement C3a