Stage-Specific Regulation of Gene Expression in Leishmania Posttranscriptional gene regulation mediates morphological, biochemical changes when Leishmania move from sandflies into humans

L eishmania is an early-branching unicellular eukaryote belonging to the order Kinetoplastidae and family Trypanosomatidae. At least 20 Leishmania spp. cause leishmaniasis, vector-borne parasitic diseases with a large spectrum of clinical symptoms that depend on the species. Leishmania infects mononuclear phagocytes, key cellular components of the immune system. Intracellular survival of these parasites within human macrophages helps them to subvert the effector and regulatory functions of these cells. Clinical manifestations of leishmaniasis are multifaceted, ranging from spontaneously resolving skin lesions to life-threatening visceral diseases, and depend on complex interactions between the host immune response and the infecting Leishmania species. Visceral leishmaniasis by L. donovani, L. infantum, or L. chagasi causes elevated morbidity and mortality. The cutaneous form is transmitted mainly by L. major, L. tropica, and L. mexicana and causes chronic skin ulcers. Mucosal leishmaniasis can be found in many Latin American countries and is caused by the L. braziliensis complex. The disease is endemic in 88 countries and is found in both tropical and subtropical regions, according to the World Heath Organization (WHO). More than 15 million people are infected, and some 350 million people are at risk. During its digenetic life cycle, Leishmania moves between the alimentary tract of the sandfly vector and the acidic phagolysosomes of mammalian macrophages. The ability of Leishmania to survive within phagolysosomes is heavily dependent on the developmental regulation of a variety of genes. Identifying the genes that are expressed preferentially during the parasite’s intracellular growth would help to elucidate the mechanisms controlling stage-specific gene regulation and intracellular survival of the parasite. Moreover, genes whose expression is modulated during the parasite’s cytodifferentiation may represent therapeutic targets. Therefore, considerable efforts are being directed toward identifying and characterizing these developmentally expressed genes and the molecular mechanisms underlying their regulation. The ongoing Leishmania major genome sequence project (www.ebi.ac.uk /parasites/leish.html) is contributing significantly to these efforts.