Citation

Plague is a rapidly lethal human disease caused by the bacterium Yersinia pestis (Yp). This study demonstrates that the Yp plasminogen activator Pla, a protease that promotes fibrin degradation, thwarts T cell-mediated defense against fully-virulent Yp. Introducing a single point mutation into the active site of Pla suffices to render fully-virulent Yp susceptible to primed T cells. Mechanistic studies reveal essential roles for fibrin during T cell-mediated defense against Pla-mutant Yp. Moreover, the efficacy of T cell-mediated protection against various Yp strains displays an inverse relationship with their levels of Pla activity. Together, these data indicate Pla functions to thwart fibrin-dependent T cell-mediated defense against plague. Other important human bacterial pathogens including staphylococci, streptococci, and borrelia, likewise produce virulence factors that promote fibrin degradation. The discovery that Yp thwarts T cell defense by promoting fibrinolysis suggests novel therapeutic approaches to amplifying T cell responses against human pathogens. Copyright 2019 American Society for Microbiology.