Bacterial Proteases as Thrombolytics and Fibrinolytics

Abstract

Proteases regulate important pathophysiological processes in human body such as homeostasis, blood
coagulation, fibrinolysis, tumor progression, etc. These biological effects of proteases largely attribute to their
applicability as therapeutic agents. Imbalance in blood coagulation and fibrinolysis, two important physiological
processes in human body, leads to thrombosis, a leading cause of cardiovascular complications including myocardial
infarction, stroke, etc. The enzymes used to dissolve thrombus (blood clot) are known as thrombolytic agents and
among them, the enzymes involving hydrolysis of fibrin called fibrinolytic agents. Thrombolytic agents can be
classified according to generation, mechanism of action, source and active site of the enzymes. Among the
commercially available thrombolytic agents, uPA and tPA are generally safe but are very expensive. On the other
hand, the bacterial streptokinase is a relatively cheap thrombolytic agent but causes undesirable side effects such as
bleeding complications. For this reason, worldwide research for potent thrombolytic agents to prevent and treat
cardiovascular diseases have been continuing. Microbes are considered as a potential source of as well as safe vectors
for expressing thrombolytic and fibrinolytic enzymes. Bacilli are one of the largest groups for this purpose. They
have been collected from different traditional fermented foods or have been produced by solid state fermentation
using appropriate nutrient substrates including different agro-industrial wastes such as rice straw, molasses, soybean
curd residues, etc. This review focuses on different bacterial proteases reported to have potential thrombolytic and
fibrinolytic activities.