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Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of alpha-1 antitrypsin

Niclasen, Louise Meinert; Olsen, Johan G.; Dagil, Robert; Zhang, Qing LU ; Sørensen, Ole E LU and Kragelund, Birthe B. (2011) In Biochemical Journal 434. p.123-132
Abstract
The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after systemic spreading. Addition of Spa to human plasma increased plasma-mediated bacterial killing and prolonged coagulation time through the intrinsic pathway of coagulation. This effect was independent of the enzymatic activity of SpeB and was mediated by a non-covalent medium-affinity binding and modification of the serpin A1AT (alpha-1 antitrypsin). Consequently, addition of A1AT to plasma increased bacterial survival. Sequestration of A1AT by SpeB... (More)
The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after systemic spreading. Addition of Spa to human plasma increased plasma-mediated bacterial killing and prolonged coagulation time through the intrinsic pathway of coagulation. This effect was independent of the enzymatic activity of SpeB and was mediated by a non-covalent medium-affinity binding and modification of the serpin A1AT (alpha-1 antitrypsin). Consequently, addition of A1AT to plasma increased bacterial survival. Sequestration of A1AT by SpeB led to enhanced contact system activation, supported by increased bacterial growth in prekallikrein deficient plasma. In a mouse model of systemic infection, administration of SpeB reduced significantly bacterial dissemination. The findings reveal an additional layer of complexity to host-microbe interactions that may be of benefit in the treatment of severe bacterial infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dissemination, innate immune system, photo cross-linking, Streptococcus, pyogenes, systemic spreading
in
Biochemical Journal
volume
434
pages
123 - 132
publisher
Portland Press Limited
external identifiers
  • wos:000287461000012
  • scopus:79251543226
ISSN
0264-6021
DOI
10.1042/BJ20100984
language
English
LU publication?
yes
id
dba98ba3-5d61-4594-bde3-168a327f6952 (old id 1878182)
date added to LUP
2011-04-01 08:35:49
date last changed
2017-10-01 03:59:49
@article{dba98ba3-5d61-4594-bde3-168a327f6952,
  abstract     = {The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after systemic spreading. Addition of Spa to human plasma increased plasma-mediated bacterial killing and prolonged coagulation time through the intrinsic pathway of coagulation. This effect was independent of the enzymatic activity of SpeB and was mediated by a non-covalent medium-affinity binding and modification of the serpin A1AT (alpha-1 antitrypsin). Consequently, addition of A1AT to plasma increased bacterial survival. Sequestration of A1AT by SpeB led to enhanced contact system activation, supported by increased bacterial growth in prekallikrein deficient plasma. In a mouse model of systemic infection, administration of SpeB reduced significantly bacterial dissemination. The findings reveal an additional layer of complexity to host-microbe interactions that may be of benefit in the treatment of severe bacterial infections.},
  author       = {Niclasen, Louise Meinert and Olsen, Johan G. and Dagil, Robert and Zhang, Qing and Sørensen, Ole E and Kragelund, Birthe B.},
  issn         = {0264-6021},
  keyword      = {dissemination,innate immune system,photo cross-linking,Streptococcus,pyogenes,systemic spreading},
  language     = {eng},
  pages        = {123--132},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of alpha-1 antitrypsin},
  url          = {http://dx.doi.org/10.1042/BJ20100984},
  volume       = {434},
  year         = {2011},
}