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Streptococcal inhibitor of complement-mediated lysis (SIC): an anti-inflammatory virulence determinant

Åkesson, Per LU ; Herwald, Heiko LU ; Rasmussen, Magnus LU ; Håkansson, Katarina LU ; Abrahamson, Magnus LU ; Hasan, Ahmed A. K.; Schmaier, Alvin H.; Mueller-Ester, Werner and Björck, Lars LU (2010) In Microbiology1994-01-01+01:00 156. p.3660-3668
Abstract
Since the late 1980s, a worldwide increase of severe Streptococcus pyogenes infections has been associated with strains of the M1 serotype, strains which all secrete the streptococcal inhibitor of complement-mediated lysis (SIC). Previous work has shown that SIC blocks complement-mediated haemolysis, inhibits the activity of antibacterial peptides and has affinity for the human plasma proteins clusterin and histidine-rich glycoprotein; the latter is a member of the cystatin protein family. The present work demonstrates that SIC binds to cystatin C, high-molecular-mass kininogen (HK) and low-molecular-mass kininogen, which are additional members of this protein family. The binding sites in HK are located in the cystatin-like domain D3 and... (More)
Since the late 1980s, a worldwide increase of severe Streptococcus pyogenes infections has been associated with strains of the M1 serotype, strains which all secrete the streptococcal inhibitor of complement-mediated lysis (SIC). Previous work has shown that SIC blocks complement-mediated haemolysis, inhibits the activity of antibacterial peptides and has affinity for the human plasma proteins clusterin and histidine-rich glycoprotein; the latter is a member of the cystatin protein family. The present work demonstrates that SIC binds to cystatin C, high-molecular-mass kininogen (HK) and low-molecular-mass kininogen, which are additional members of this protein family. The binding sites in HK are located in the cystatin-like domain D3 and the endothelial cell-binding domain D5. Immobilization of HK to cellular structures plays a central role in activation of the human contact system. SIC was found to inhibit the binding of HK to endothelial cells, and to reduce contact activation as measured by prolonged blood clotting time and impaired release of bradykinin. These results suggest that SIC modifies host defence systems, which may contribute to the virulence of S. pyogenes strains of the M1 serotype. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Microbiology1994-01-01+01:00
volume
156
pages
3660 - 3668
publisher
MAIK Nauka/Interperiodica
external identifiers
  • wos:000285806200015
  • scopus:78650039436
  • pmid:20705662
ISSN
1465-2080
DOI
10.1099/mic.0.039578-0
language
English
LU publication?
yes
id
4fbf4793-04d0-426e-aae8-ac17a529a028 (old id 1811560)
date added to LUP
2011-03-02 13:40:26
date last changed
2018-06-17 03:17:49
@article{4fbf4793-04d0-426e-aae8-ac17a529a028,
  abstract     = {Since the late 1980s, a worldwide increase of severe Streptococcus pyogenes infections has been associated with strains of the M1 serotype, strains which all secrete the streptococcal inhibitor of complement-mediated lysis (SIC). Previous work has shown that SIC blocks complement-mediated haemolysis, inhibits the activity of antibacterial peptides and has affinity for the human plasma proteins clusterin and histidine-rich glycoprotein; the latter is a member of the cystatin protein family. The present work demonstrates that SIC binds to cystatin C, high-molecular-mass kininogen (HK) and low-molecular-mass kininogen, which are additional members of this protein family. The binding sites in HK are located in the cystatin-like domain D3 and the endothelial cell-binding domain D5. Immobilization of HK to cellular structures plays a central role in activation of the human contact system. SIC was found to inhibit the binding of HK to endothelial cells, and to reduce contact activation as measured by prolonged blood clotting time and impaired release of bradykinin. These results suggest that SIC modifies host defence systems, which may contribute to the virulence of S. pyogenes strains of the M1 serotype.},
  author       = {Åkesson, Per and Herwald, Heiko and Rasmussen, Magnus and Håkansson, Katarina and Abrahamson, Magnus and Hasan, Ahmed A. K. and Schmaier, Alvin H. and Mueller-Ester, Werner and Björck, Lars},
  issn         = {1465-2080},
  language     = {eng},
  pages        = {3660--3668},
  publisher    = {MAIK Nauka/Interperiodica},
  series       = {Microbiology1994-01-01+01:00},
  title        = {Streptococcal inhibitor of complement-mediated lysis (SIC): an anti-inflammatory virulence determinant},
  url          = {http://dx.doi.org/10.1099/mic.0.039578-0},
  volume       = {156},
  year         = {2010},
}