Thrombin-activatable fibrinolysis inhibitor is degraded by Salmonella enterica and Yersinia pestis.
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.
Valls Serón
M
M
Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. M.Vallsseron@amc.uva.nl
Haiko
J
J
DE Groot
P G
PG
Korhonen
T K
TK
Meijers
J C M
JC
D001426:Bacterial Proteins / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D025901:Carboxypeptidase B2 / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D010949:Plasma / Q000382:microbiology; D010957:Plasmids / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D018272:Porins / Q000378:metabolism; D012480:Salmonella Infections / Q000150:complications / Q000378:metabolism*; D019779:Salmonella enterica / Q000378:metabolism*; D013997:Time Factors; D015009:Yersinia Infections / Q000150:complications / Q000378:metabolism*; D015010:Yersinia pestis / Q000378:metabolism*
D001426:Bacterial Proteins; D018272:Porins; C405564:ompT protein, bacteria; D010450:Endopeptidases; C411337:PgtE protein, Salmonella enterica; D025901:Carboxypeptidase B2; C078140:Pla protease, Yersinia pestis; D010960:Plasminogen Activators