Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of a-1 antitrypsin
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Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of a-1 antitrypsin. / Meinert Niclasen, Louise; Olsen, Johan G; Dagil, Robert; Qing, Zhang; Sørensen, Ole E; Kragelund, Birthe B.
I: Biochemical Journal, Bind 434, Nr. 1, 2011, s. 123-32.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of a-1 antitrypsin
AU - Meinert Niclasen, Louise
AU - Olsen, Johan G
AU - Dagil, Robert
AU - Qing, Zhang
AU - Sørensen, Ole E
AU - Kragelund, Birthe B
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Bacterial Proteins
KW - Chemotaxis
KW - Exotoxins
KW - Humans
KW - Leukocytes, Mononuclear
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Protein Binding
KW - Streptococcal Infections
KW - Streptococcus pyogenes
KW - alpha 1-Antitrypsin
U2 - 10.1042/BJ20100984
DO - 10.1042/BJ20100984
M3 - Journal article
C2 - 21080914
VL - 434
SP - 123
EP - 132
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 1
ER -
ID: 33224048