Activation of blood clotting factors by microbial proteinases

Abstract

There are very few reports on the involvement of bacterial proteinases on the blood clotting system using both human plasma and purified clotting factors. We studied whether microbial proteinases from the opportunistic pathogens Candida albicans, Pseudomonas aeruginosa and Serratia marcescens activate the blood clotting cascade by using normal human plasma, human plasmas deficient in clotting factor XII or X, and also by using purified clotting factors XII, X and prothrombin. All proteinases tested activated either clotting factor XII or prothrombin in vitro, thus resulting in generation of thrombin. Clotting factor X was converted to the active form (Xa) by both Candida and Pseudomonas proteinases, but not by Serratia proteinase. These results suggest that peripheral and systemic blood circulation may be impaired by activation of the blood clotting cascade by microbial infections, especially in septic patients, which would enhance disseminated intravascular coagulation and multi-organ failure.

EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V

“…The proteases from the opportunistic pathogens Candida albicans, Pseudomonas aeruginosa and S. marcescens activate the blood-clotting cascade. These proteases apparently convert factor X or factor XII to the respective active forms, X a or XII a (Kaminishi et al, 1994). The finding that EspP* secreted by EHEC is able to degrade coagulation factor V indicates that this pathogen could also influence the blood-clotting cascade.…”

Extracellular proteinases of Candida species pathogenic yeasts

“…Pathological fibrin clot formation (activation of factors X, XII and prothrombin) 78 Increased permeabilization of blood vessels through kinin generation (factor XII activation, HK and LK degradation) [79][80][81][82] Host protease inhibitors Tissue damage, dissemination Damage of host tissue by its own enzymes, resulting from α2-macroglobulin, cystatin A and α1-protease inhibitor degradation [83][84][85] Antifungal peptides Immune evasion Degradation and inactivation of histatin 5 and cathelicidin LL-37 [86][87][88] Host defense cells Immune evasion Decreased phagocytosis 89 Host defense cells Activation of the inflammatory response Direct interleukin-1β activation 90 HK, high-molecular-mass kininogen; LK, low-molecular-mass kininogen.…”

“…This mechanism may underlie septic coagulation and account for the insufficient peripheral circulation that can occur during infections. 78,83 In vitro, factor XII, factor X and prothrombin have been shown to be activated by C. albicans Sap2 78,79,83 and factor X and prothrombin by C. parapsilosis Sapp1. 38,39 Factor XII can be adsorbed onto the blood vessel walls along with prekallikrein (a zymogen of plasma kallikrein) and a non-enzymatic fac- activate kinin production via two mechanisms: (i) the activation of factor XII, as shown for Sap2, 79 and (ii) direct proteolytic cleavage of kininogen molecules.…”

Activation of prothrombin by ASP, a serine protease released from Aeromonas sobria

“…Cysteine proteases (gingipains-R) produced by Porphyromonas gingivalis [11], and metalloproteases from Staphylococcus aureus [20] or Vibrio vulnificus [21], have been shown to activate human prothrombin. Metalloproteases from Serratia marcescens and Pseudomonas aeruginosa were reported to be capable of releasing thrombin activity from bovine prothrombin [22]. No serine protease of bacterial origin has been reported as a prothrombin activator, thus ASP is currently the only bacterial serine protease shown to possess this ability.…”