Yersinia pestis escapes entrapment in thrombi by targeting platelet function.

Samantha G Palace, Olga Vitseva, Megan K Proulx, Jane E Freedman, Jon D Goguen, Milka Koupenova

Journal of thrombosis and haemostasis : JTH 2020 Dec

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Platelets are classically recognized for their role in hemostasis and thrombosis. Recent work has demonstrated that platelets can also execute a variety of immune functions. The dual prothrombotic and immunological roles of platelets suggest that they may pose a barrier to the replication or dissemination of extracellular bacteria. However, some bloodborne pathogens, such as the plague bacterium Yersinia pestis, routinely achieve high vascular titers that are necessary for pathogen transmission. It is not currently known how or if pathogens circumvent platelet barriers to bacterial dissemination and replication. We sought to determine whether extracellular bloodborne bacterial pathogens actively interfere with platelet function, using Y pestis as a model system. The interactions and morphological changes of human platelets with various genetically modified Y pestis strains were examined using aggregation assays, immunofluorescence, and scanning electron microscopy. Yersinia pestis directly destabilized platelet thrombi, preventing bacterial entrapment in fibrin/platelet clots. This activity was dependent on two well-characterized bacterial virulence factors: the Y pestis plasminogen activator Pla, which stimulates host-mediated fibrinolysis, and the bacterial type III secretion system (T3SS), which delivers bacterial proteins into the cytoplasm of targeted host cells to reduce or prevent effective immunological responses. Platelets intoxicated by the Y pestis T3SS were unable to respond to prothrombotic stimuli, and T3SS expression decreased the formation of neutrophil extracellular traps in platelet thrombi. These findings are the first demonstration of a bacterial pathogen using its T3SS and an endogenous protease to manipulate platelet function and to escape entrapment in platelet thrombi. © 2020 International Society on Thrombosis and Haemostasis.

Citation

Samantha G Palace, Olga Vitseva, Megan K Proulx, Jane E Freedman, Jon D Goguen, Milka Koupenova. Yersinia pestis escapes entrapment in thrombi by targeting platelet function. Journal of thrombosis and haemostasis : JTH. 2020 Dec;18(12):3236-3248