Characterization of regulated genes of Leishmania amazonensis dependent of arginase activity

Abstract

The parasite belonging to Leishmania genus presents two main morphological forms during the life cycle. The promastigotes forms are extracellular, elongated and flagellated cells that proliferate in the digestive tract from the invertebrate host. The amastigotes forms are intracellular with non-apparent flagellum that proliferate in the mononuclear phagocytic system, being the macrophage the main cell from vertebrate host. Our research group has been studying the polyamine pathway in Leishmania and characterizing the role of arginase, which uses the amino acid L-arginine to produce urea and ornithine, a precursor of polyamines related to parasite replication. RNA-seq has been used to describe how stability and processing of mRNA can occur during the mechanisms of gene expression regulation. We recently described the existence of a differential gene expression regulation in the comparison of promastigotes from L. amazonensis wild type (La-WT) and L. amazonensis arginase knockout (La-arg-). Among the differentially expressed genes, two transcripts showed the highest level of regulation, an up-regulated hypothetical protein (LmxM.15.1520), and a down-regulated RNA binding protein (RBP) (LmxM.07.0990). Then, in the present project, we intend to characterize both, that will provide important knowledge about arginase activity and how Leishmania is able to modulate the mechanisms of gene expression regulation to subvert the absence of an enzyme activity to allow the parasite survival.