Open AccessPolyphosphate and omptins: novel bacterial procoagulant agents
Author(s) -
Yun Thomas H.,
Morrissey James H.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00884.x
Subject(s) - yersinia pestis , proteases , coagulation , microbiology and biotechnology , plasmin , yersinia , fibrinolysis , biochemistry , chemistry , tissue factor pathway inhibitor , biology , enzyme , tissue factor , bacteria , virulence , medicine , genetics , psychiatry , gene
• Introduction • Inorganic polyP in nature • PolyP modulates haemostasis ‐ PolyP alters fibrin clot structure and stability ‐ Degradation of polyP in plasma ‐ PolyP activates the contact pathway• Bacterial omptins and coagulation ‐ Omptin structure ‐ Evolution of Y. pestis and its life cycle ‐ Expression of Pla increases Y. pestis virulence ‐ Plasminogen activation by Pla ‐ TFPI inactivation and factor VII activation by Pla ‐ Other functions of PlaDerangement of the blood clotting system contributes strongly to multiple organ failure in severe sepsis. In this review, we examine two microbial modulators of the clotting system: polyphosphates and omptins. Polyphosphates are linear polymers of inorganic phosphate that are abundant in the acidocalcisomes of prokaryotes and unicellular organisms as well as in the dense granules of human platelets. Polyphosphates modulate haemostasis by: (1) triggering clotting via the contact pathway; (2) accelerating the activation of coagulation factor V (a key cofactor in blood clotting) and (3) causing fibrin to form clots whose fibrils are thicker and more resistant to fibrinolysis. While polyphosphates are found in all prokaryotes, omptins have a more limited distribution among certain Gram‐negative species. Omptins are outer membrane aspartyl proteases which were recently found to proteolytically inactivate tissue factor pathway inhibitor (TFPI), the main inhibitor of the initiation phase of blood clotting. Omptin activity against TFPI requires lipopolysaccharide without O‐antigen (rough LPS) such as is found on the surface of Yersinia pestis , the etiologic agent of plague. Interestingly, expression of Pla, the Yersinia pestis omptin, has a demonstrated virulence role in converting plasminogen into the fibrinolytic enzyme plasmin, which would seemingly antagonize any procoagulant effect of TFPI inactivation. However, since the rate of TFPI inactivation is much higher than the rate of plasminogen activation, we suggest that Pla may have a dual function in supporting the bubonic form of plague which is unique to Yersinia pestis .