Biochemistry of the Leishmania species

Abstract

The Leishmania spp. are intracellular protozoal parasites which belong to the family of hemoflagellates that includes the highly infectious and well-known trypanosomes. Organisms of this genus are responsible for one of the major classes of communicable diseases of the world. The flagellated protozoan has a digenic life cycle; in the alimentary tract of its insect vector, the blood-sucking sandfly, it exists extracellularly as the motile promastigote form, whereas in the phagolysosomal system of mammalian macrophages, it exists intracellularly as the nonmotile amastigote form. The amastigote has apparently adapted to survive and multiply in an acid environment like that provided by the phagolysosome of polymorphonuclear leukocytes. In contrast, promastigotes perform their metabolic functions optimally at neutral pH. Little is known about the key enzymes involved in the critical phases of the organism's life cycle or in the host-parasite interaction. This review focuses mainly on the enzymes and metabolic machinery of the Leishmania spp. responsible for the various forms of leishmaniasis in humans: visceral leishmaniasis (kala azar), mucocutaneous leishmaniasis, and cutaneous leishmaniasis. We summarize the results of reports which describe the enzymes and proteins that are localized to the outer surface of the various species of Leishmania. Emphasis is placed on the predominant cell surface acid phosphatase which has the ability to inhibit markedly the oxygen burst and the production of O2- by stimulated phagocytes. The mechanism of action of the leishmanial acid phosphatase seems to involve reductions in second-messenger levels in phosphatase-treated phagocytes. In addition, this review attempts to consolidate existing knowledge about the properties and possible functions of nucleotidases, proteases, protein kinases, and the glycoproteinaceous excreted factor produced by the Leishmania spp. Finally, we review the metabolic capabilities of the Leishmania spp., including the pathways of carbohydrate, fat, amino acid, purine, and pyrimidine metabolism, keeping in mind their possible significance to the host-parasite relationship.