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Thrombin‐activatable fibrinolysis inhibitor is degraded by Salmonella enterica and Yersinia pestis
Author(s) -
VALLS SERÓN M.,
HAIKO J.,
DE GROOT P. G.,
KORHONEN T. K.,
MEIJERS J. C. M.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2010.04014.x
Subject(s) - yersinia pestis , salmonella enterica , plasmin , microbiology and biotechnology , proteases , fibrinolysis , thrombin , salmonella , yersinia , fibrin , chemistry , thrombomodulin , coagulation , biology , bacteria , biochemistry , enzyme , immunology , medicine , virulence , platelet , genetics , psychiatry , gene
Summary. Background : Pathogenic bacteria modulate the host coagulation system to evade immune responses or to facilitate dissemination through extravascular tissues. In particular, the important bacterial pathogens Salmonella enterica and Yersinia pestis intervene with the plasminogen/fibrinolytic system. Thrombin‐activatable fibrinolysis inhibitor (TAFI) has anti‐fibrinolytic properties as the active enzyme (TAFIa) removes C‐terminal lysine residues from fibrin, thereby attenuating accelerated plasmin formation. Results : Here, we demonstrate inactivation and cleavage of TAFI by homologous surface proteases, the omptins Pla of Y. pestis and PgtE of S. enterica . We show that omptin‐expressing bacteria decrease TAFI activatability by thrombin‐thrombomodulin and that the anti‐fibrinolytic potential of TAFIa was reduced by recombinant Escherichia coli expressing Pla or PgtE. The functional impairment resulted from C‐terminal cleavage of TAFI by the omptins. Conclusions : Our results indicate that TAFI is degraded directly by the omptins PgtE of S. enterica and Pla of Y. pestis . This may contribute to the ability of PgtE and Pla to damage tissue barriers, such as fibrin, and thereby to enhance spread of S. enterica and Y. pestis during infection.