Searching for genes potentially involved in virulence control in Leishmania major

Abstract

Human infections with Leishmania spp give rise to a spectrum of clinical manifestations ranging from tegumentary lesions to a visceral disease. In this context, the identification / characterization of genes or groups of genes that affect the pattern of virulence of the parasite is important to improve understanding of the pathogenic mechanisms. Previous studies conducted in our laboratory described the attenuation of virulence due to overexpression of the SL RNA in transfectants of Leishmania (L.) major and Leishmania (V.) braziliensis in a murine model. Evaluation of global changes in gene expression profile was conducted to understand the phenotype. These comparative analyses allowed the identification of genes that were over- or under-expressed on the attenuated mutants; these genes may individually contribute to the virulence behavior. To verify this hypothesis we will investigate the effect of a group of these genes (three to six) found as under- or over-expressed. The genes will be cloned into a Leishmania expression vector and transfected into two L. (L.) major strains (virulent and nonvirulent strains in susceptible mice) to analyze the infection pattern in vitro and in vivo using peritoneal macrophages and susceptible mice, BALB/c.