Structure and function of infective stage proteins of Leishmania.

Introduction Parasitic protozoa of the genus Leishmania are causative agents of the broad spectrum of human diseases termed the leishmaniases, which are prevalent in sub-tropical and tropical regions of the world 111. These unicellular organisms are members of the family Trypanosomatidae, a group which is characterized (at the molecular level) by a number of unusual mechanisms for gene regulation, including polycistronic transcription of multicopy gene families, post-transcriptional processing of precursor RNA molecules by trans-splicing and RNA editing in mitochondria [2-51. Viability of Leishmania is dependent on the organism’s successful adaptation to both extracellular and intracellular habitats; components of the parasite surface coat are essential for this process. In the mammalian host, infection is the consequence of inoculation of parasites through the skin and uptake by host macrophages. The inoculated organisms are flagellated promastigotes; these develop within the digestive tract of the phlebotomine sandfly vector but must undergo differentiation from dividing, non-infective (procyclic) to non-dividing, infective (metacyclic) parasites before entry into the host [6-91. Acquisition of infectivity in the vector is accompanied by structural modification of carbohydrate components of the parasite surface coat to form a thick glycocalyx [lo-121. Functionally, this surface ensures the ability of the parasite to resist lysis by complement and enter host macrophages by receptor-mediated phagocytosis. Here, the parasites differentiate a second time into aflagellated amastigotes, which are capable of survival within the parasitophorous vacuole of the macrophage [ 11. Uptake by a blood-feeding sandfly and transformation back to flagellated promastigotes completes the parasite life cycle.