Abstract

Plasmodium sporozoites are transmitted to mammals by anopheline mosquitoes and first infect the liver, where they transform into replicative exoerythrocytic forms, which subsequently release thousands of merozoites that invade erythrocytes and initiate the malaria disease. In some species, sporozoites can transform into dormant hypnozoites in the liver, which cause malaria relapses upon reactivation. Transmission from the insect vector to a mammalian host is a critical step of the parasite life cycle, and requires tightly regulated gene expression. Sporozoites are formed inside oocysts in the mosquito midgut and become fully infectious after colonization of the insect salivary glands, where they remain quiescent until transmission. Parasite maturation into infectious sporozoites is associated with reprogramming of the sporozoite transcriptome and proteome, which depends on multiple layers of transcriptional and post-transcriptional regulatory mechanisms. An emerging scheme is that gene expression in Plasmodium sporozoites is controlled by alternating waves of transcription activity and translational repression, which shape the parasite RNA and protein repertoires for successful transition from the mosquito vector to the mammalian host.

Highlights

  • Malaria is caused by protozoan parasites of the Plasmodium genus, and remains a major global health problem in endemic countries

  • We summarize the current understanding of the gene regulation mechanisms underpinning Plasmodium maturation into highly infectious sporozoites capable of invading the mammalian host hepatocytes, establish parasite reservoirs and transmit the disease

  • Combined with the nuclear localization of the protein in P. berghei sporozoites and exoerythrocytic forms (EEFs) (Silvie et al, 2008), we propose that SLARP functions as a master transcriptional regulator in sporozoites and liver stages (Figure 1)

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Summary

Introduction

Malaria is caused by protozoan parasites of the Plasmodium genus, and remains a major global health problem in endemic countries. Studies of gene regulation in the malaria parasite have been greatly facilitated by the availability of genome sequence data, as illustrated by the first identification of a specific transcription factor (Myb1) in P. falciparum (Boschet et al, 2004; Gissot et al, 2005), rapidly followed by the discovery of the plant-like Apetala-2 (AP2) domain family of DNA-binding proteins (Balaji et al, 2005).

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