Abstract
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.
Highlights
The innate immune system provides a rapid and nonspecific defense at biological boundaries prone to infection
Multiplication of S. pyogenes in Human Plasma Is Controlled by Complement and Contact Systems—To investigate the importance of contact activation in controlling bacterial growth, the S. pyogenes isolate AP1 was cultivated in human plasma deficient of the various contact factors
As compared with normal plasma, the growth rate was enhanced in plasma that was deficient of plasma kallikrein (PK), factor XII (FXII), or high molecular weight kininogen (HK) (Fig. 1A)
Summary
The innate immune system provides a rapid and nonspecific defense at biological boundaries prone to infection. 400 l of the bacterial solution (8 ϫ 107 cfu) was incubated with 400 l PBS or plasma together with various concentrations of protein SIC for 1 h at 37 °C. After 8 h of growth, the bacterial numbers were significantly higher in plasma lacking either of these contact factors (Fig. 1A, inset), suggesting that the generation of antibacterial peptide fragments from HK was affected.
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