Identification of Leptospira proteases involved in the degradation of extracellular matrix proteins

Abstract

Leptospirosis, a zoonosis widely spread around the world, is caused by spirochetes of the genus Leptospira. Highly frequent in tropical and subtropical areas, the disease represents an important public health problem. In the last years, researches have been focused on factors related to the pathogenesis of the disease. Pathogenic leptospires have the ability to circumvent host´s defense mechanisms by avoiding complement mediated lysis. Moreover, they express membrane proteins that interact with cells and extracellular matrix proteins from the host. The aim of this project is to evaluate the secretion of proteases by different Leptospira species capable of directly degrading extracellular matrix proteins. Previous assays performed by our group have demonstrated that proteins secreted by pathogenic leptospires are able to cleave and inactivate key molecules of the complement system. The ability to cleave conjunctive tissue molecules may certainly contribute to invasion and tissue destruction observed upon infection with these bacteria. Among the proteases secreted by pathogenic leptospires, we selected the metalloprotease NprT from the thermolysin family to perform proteolytic activity assays. This protease shares a high degree of similarity with proteins present in other pathogens, known to degrade extracellular matrix components, thus representing a relevant candidate for substrates such as laminin, fibronectin, collagens, elastin and fibrinogen. The identification and characterization of proteases capable of cleaving extracellular matrix proteins is of great relevance and may contribute to the development of therapeutic strategies to fight the disease.