TY - JOUR
T1 - Antibacterial activity of the contact and complement systems is blocked by SIC, a protein secreted by Streptococcus pyogenes.
AU - Frick, Inga-Maria
AU - Shannon, Oonagh
AU - Åkesson, Per
AU - Mörgelin, Matthias
AU - Collin, Mattias
AU - Schmidtchen, Artur
AU - Björck, Lars
PY - 2011
Y1 - 2011
N2 - Recent studies have shown that activation of the complement and contact systems results in the generation of antibacterial peptides. Streptococcus pyogenes, a major bacterial pathogen in humans, exists in more than one hundred 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 to explain the high frequency of severe S. pyogenes infections caused by isolates of the M1 serotype.
AB - Recent studies have shown that activation of the complement and contact systems results in the generation of antibacterial peptides. Streptococcus pyogenes, a major bacterial pathogen in humans, exists in more than one hundred 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 to explain the high frequency of severe S. pyogenes infections caused by isolates of the M1 serotype.
U2 - 10.1074/jbc.M110.178350
DO - 10.1074/jbc.M110.178350
M3 - Article
C2 - 21068386
SN - 1083-351X
VL - 286
SP - 1331
EP - 1340
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
ER -