| Summary: | The Gram-negative bacterium <i>Yersinia pestis</i> causes plague, a fatal flea-borne anthropozoonosis, which can progress to aerosol-transmitted pneumonia. <i>Y. pestis</i> overcomes the innate immunity of its host thanks to many pathogenicity factors, including plasminogen activator, Pla. This factor is a broad-spectrum outer membrane protease also acting as adhesin and invasin. <i>Y. pestis</i> uses Pla adhesion and proteolytic capacity to manipulate the fibrinolytic cascade and immune system to produce bacteremia necessary for pathogen transmission via fleabite or aerosols. Because of microevolution, <i>Y. pestis</i> invasiveness has increased significantly after a single amino-acid substitution (I259T) in Pla of one of the oldest <i>Y. pestis</i> phylogenetic groups. This mutation caused a better ability to activate plasminogen. In paradox with its fibrinolytic activity, Pla cleaves and inactivates the tissue factor pathway inhibitor (TFPI), a key inhibitor of the coagulation cascade. This function in the plague remains enigmatic. Pla (or <i>pla</i>) had been used as a specific marker of <i>Y. pestis</i>, but its solitary detection is no longer valid as this gene is present in other species of <i>Enterobacteriaceae</i>. Though recovering hosts generate anti-Pla antibodies, Pla is not a good subunit vaccine. However, its deletion increases the safety of attenuated <i>Y. pestis</i> strains, providing a means to generate a safe live plague vaccine.
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