Abstract Number: PB1789
Meeting: ISTH 2020 Congress
Background: The surface anchored M1 protein is a major virulence determinant of a highly prevalent and virulent Group A streptococcus (GAS) strain, M1T1. During early infection M1 is cleaved from the cell surface resulting in soluble M1 at the site of infection. Fibrin formation is an essential part of innate immunity and a protective fibrin biofilm covers the external surface of clots acting as the first line of defense. Within the clot the fibrin network traps bacteria to limit dissemination and reduce the severity of invasive infections. M1 is known to form a supramolecular complex with fibrinogen however the impact of this on fibrin formation and structure is unknown.
Aims: Investigate the impact of GAS M1 protein on fibrin clot formation, structure and fibrinolytic potential.
Methods: Fibrin clots incorporating recombinant M1 (rM1) were made by the addition of thrombin to human blood, plasma and purified fibrinogen. Fibrin structure was assessed using imaging techniques (confocal microscopy and scanning electron microscopy), permeation assays (gel porosity) and bacterial migration assays. Fibrin clot formation, mechanical strength and lysis rates were measured kinetically using thromboelastography (ROTEM).
Results: rM1 (0.47-60 µg/ml) increased clotting rates to produce heterogeneous clots with irregular fibre bundles and compacted fibrin (Figure 1A) and increased porosity (above 15 µg/ml rM1) up to 12-fold at 60 µg/ml (Figure 1B). rM1 disrupted formation of the protective fibrin biofilm (Figure 2) and reduced mechanical clot strength to undetectable levels above rM1 concentrations of 15 µg/ml. Lysis times for purified and plasma clots incorporating rM1 were reduced up to 2-fold.
Conclusions: GAS strains of M1-type are commonly associated with invasive infections. M1-bound fibrinogen at infection sites may contribute to the severity of infection by forming fibrin clots with a compromised protective film at the surface, that are mechanically weaker, more porous, and less resistant to lysis by plasmin.
To cite this abstract in AMA style:Cherrington S, Hardy L, Francis RJ, Macrae F, Duval C, Ariens RA, Maqbool A, Philippou H, Thelwell C. M1 Protein from Group A Streptococcus Regulates Fibrin Clot Formation, Structure and Fibrinolytic Potential [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/m1-protein-from-group-a-streptococcus-regulates-fibrin-clot-formation-structure-and-fibrinolytic-potential/. Accessed November 30, 2021.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/m1-protein-from-group-a-streptococcus-regulates-fibrin-clot-formation-structure-and-fibrinolytic-potential/