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

Louise Meinert Niclasen , Johan G. Olsen , Robert Dagil , Zhang Qing , Ole E Sørensen , Birthe B. Kragelund (1)

1 Department of Biology [Copenhagen]

The Streptococcus pyogenes cysteine protease, SpeB, 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 alpha-1 antitrypsin. Consequently, supplement of alpha-1 antitrypsin to plasma increased bacterial survival. Sequestration of alpha-1 antitrypsin 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 significantly reduced bacterial dissemination. The findings reveal an additional layer of complexity to host-microbe interactions which may be of benefit in treatment of severe bacterial infections.

Mots clés: Life Sciences

Louise Meinert Niclasen, Johan G. Olsen, Robert Dagil, Zhang Qing, Ole E Sørensen, et al.. Streptococcal pyrogenic exotoxin B (SpeB) boosts the contact system via binding of alpha-1 antitrypsin. Biochemical Journal, 2011, 434 (1), pp.123-132. ⟨10.1042/BJ20100984⟩. ⟨hal-00560689⟩