M1 protein from group A Streptococcus affects fibrin clot formation, structure, and fibrinolytic potential

Le résumé fourni par la source

(GAS). During infection, M1 is cleaved from the cell surface by host and bacterial proteases resulting in soluble M1 at the site of infection. M1 forms a supramolecular complex with host fibrinogen. We hypothesize that this supramolecular complex affects the formation of fibrin clots. Fibrin formation is an essential part of innate immunity, sealing off infections to limit bacteria spreading. The effects of recombinant M1 (rM1) were assessed in fibrin clots made from whole blood, plasma, or purified fibrinogen incubated in thrombin by a semiautomated coagulation analyzer, permeation studies, confocal microscopy, and scanning electron microscopy. Clotting and lysis profiles (with plasminogen activators and plasminogen) were investigated using microtiter plate assays and kinetically with rotational thromboelastography. Factor XIII crosslinking was quantified using commercial kits and sodium dodecyl sulfate-polyacrylamide gel electrophoresis densitometry analysis. This study demonstrated that rM1-bound (0.47-60 μg/mL) fibrinogen produced clots with remarkably different structures and properties compared with clots without rM1. Inclusion of rM1 formed heterogeneous clots with irregular fiber bundles and compacted fibrin. Formation of the protective fibrin film was disrupted by rM1. Furthermore, mechanical strength of fibrin clots was reduced, and the fibrin networks were more porous with increased fluid permeability. Fibrin clots formed using whole blood incorporating rM1 were more susceptible to lysis by plasmin. GAS strains of M1 type are often associated with invasive infections; the impact of M1 on fibrin structure could contribute to the severity of GAS infection by compromising the fibrin barrier that limits bacterial proliferation and migration.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.