Plasmodium

Abstract

Malaria is the most important parasitic disease worldwide in terms of numbers of affected people and mortality. It is caused by parasites of the genus Plasmodium, which have a complex life cycle including insect vectors that are in the case of human malaria exclusively Anopheles mosquitoes. To date the genomes of several Plasmodium species have been sequenced. The overall genome organization is rather conserved, but highly divers species-specific gene families have been identified as well. The different life cycle stages exhibit a very variable morphology reflecting their respective needs. The change in cell shape during development is genetically inherited, but epigenetic factors also appear to play an important role. In the vertebrate host cell invasion and egress are crucial steps for the survival of the parasite and have evolved to highly orchestrated events, and some molecular details have been deciphered to date. Invasion occurs by invagination of the host cell membrane, and the parasite finally resides in a parasitophorous vacuole. From there it controls the behavior of its host cell by secretion of proteins into the host cell cytoplasm and to its surface. Exposed parasite proteins at the surface of an infected red blood cell allow cytoadherence and are responsible for the pathogenicity of a Plasmodium infection. Egress is a two-step process initiated by the rupture of the parasitophorous vacuole membrane and followed by disintegration of the host cell membrane that involves the activation of proteases, kinases, and membrane lytic enzymes. Recent discoveries revealed completely new parasite strategies to switch from asexual to sexual development during the blood stage and to avoid elimination by cytosolic immune responses of host cells during infection of hepatocytes.