Indentification and characterization of proteins of Leptospira interrogans involved in host-pathogen interactions

Abstract

Leptospirosis is an important global zoonosis that has been recently considered a neglected tropical disease. According to the World Health Organization, the number of annual clinical cases remains underestimated due to the wide spectrum of symptoms presented by patients and the lack of an efficient diagnostic. To date, there is not a good protective vaccine. The identification of outer membrane proteins, well conserved among pathogenic leptospiral strains, is the main focus of the currently research to elucidate mechanisms of pathogenesis. These proteins are most probably involved in the interactions of leptospires with the external environmental, and may act as targets for the host immune system. By employing the genome sequences of Leptospira interrogans and bioinformatics tools, our group has identified several membrane proteins that interact with extracellular matrix (ECM) components with possible role in the bacterial adhesion, proteins that interact with fibrinolytic system plasminogen/plasmin (PLG/PLA) and could act in the invasion process, and proteins that bind complement regulators and may participate in the leptospiral immune evasion. Considering the above stated, the present project aims: (i) identification, cloning, protein expression and purification of six novel predicted membrane proteins; these proteins will be characterized for their immunogenic activities in animal model and their interactions with ECM and serum host components; (ii) analysis of possible implications of PLA generation within bacterial surface; (iii) evaluation of interaction of leptospires and recombinant proteins with serum fibrinogen and implications for the fibrin (clot) formation, bearing in mind that severe leptospirosis produces multiple hemorrhage focus. (AU)