Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of alpha-1 antitrypsin
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1878182
- author
- Niclasen, Louise Meinert ; Olsen, Johan G. ; Dagil, Robert ; Zhang, Qing LU ; Sørensen, Ole E LU and Kragelund, Birthe B.
- organization
- publishing date
- 2011
- 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
- external identifiers
-
- wos:000287461000012
- scopus:79251543226
- pmid:21080914
- 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
- 2016-04-01 12:53:23
- date last changed
- 2022-01-27 08:07:09
@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}}, keywords = {{dissemination; innate immune system; photo cross-linking; Streptococcus; pyogenes; systemic spreading}}, language = {{eng}}, pages = {{123--132}}, publisher = {{Portland Press}}, 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}}, doi = {{10.1042/BJ20100984}}, volume = {{434}}, year = {{2011}}, }