Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of a-1 antitrypsin
Research output: Contribution to journal › Journal article › Research › peer-review
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 SpeB 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 (a-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.
Original language | English |
---|---|
Journal | Biochemical Journal |
Volume | 434 |
Issue number | 1 |
Pages (from-to) | 123-32 |
Number of pages | 10 |
ISSN | 0264-6021 |
DOIs | |
Publication status | Published - 2011 |
- Animals, Bacterial Proteins, Chemotaxis, Exotoxins, Humans, Leukocytes, Mononuclear, Male, Mice, Mice, Inbred BALB C, Protein Binding, Streptococcal Infections, Streptococcus pyogenes, alpha 1-Antitrypsin
Research areas
ID: 33224048