Interaction of outer membrane proteins from Leptospira with human vitronectin

Abstract

Leptospirosis, caused by pathogenic bacteria of the genus Leptospira, represents an important public health problem in underdeveloped tropical countries. Rodents are the main urban reservoirs of the disease. Leptospires enter the host through breaches in the skin as well as through mucous membranes and rapidly spread in the organism reaching several organs. Efficient colonization is achieved by their ability to escape the natural immune defense mechanisms of the body. Our group research is focused on the identification of immune evasion strategies employed by pathogenic leptospires, notably to escape complement-mediated lysis. In a previous project financed by FAPESP, we have demonstrated that a number of serovars, belonging to different Leptospira species, interact with human vitronectin, a glycoprotein present in the extracellular matrix and in the plasma involved in cellular migration, tissue repair and regulation of the terminal pathway of the complement system. We have also identified leptospiral membrane proteins that probably mediate this interaction. In this project we aim to further evaluate the interaction between vitronectin and the leptospiral surface proteins LigB and LcpA. Functional characterization of these molecules is of great relevance since they are promising vaccine candidates. Moreover, unraveling novel mechanisms used by this pathogen to survive in the host may aid our understanding of aspects related to the prevention of the disease.