Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity

Abstract

Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito—early and late oocysts containing midgut sporozoites, and the mature, infectious salivary gland sporozoites. Despite the morphological similarity between midgut and salivary gland sporozoites, their proteomes are markedly different, in agreement with their increase in hepatocyte infectivity. The different sporozoite proteomes contain a large number of stage specific proteins whose annotation suggest an involvement in sporozoite maturation, motility, infection of the human host and associated metabolic adjustments. Analyses of proteins identified in the P. falciparum sporozoite proteomes by orthologous gene disruption in the rodent malaria parasite, P. berghei, revealed three previously uncharacterized Plasmodium proteins that appear to be essential for sporozoite development at distinct points of maturation in the mosquito. This study sheds light on the development and maturation of the malaria parasite in an Anopheles mosquito and also identifies proteins that may be essential for sporozoite infectivity to humans. Human malaria is caused by Plasmodium falciparum, a unicellular protozoan parasite that is transmitted by Anopheles mosquitoes. An infectious mosquito injects saliva containing sporozoite forms of the parasite and these then migrate from the skin to the liver, where they establish an infection. Many intervention strategies are currently focused on preventing the establishment of infection by sporozoites. Clearly, an understanding of the biology of the sporozoite is essential for developing new intervention strategies. Sporozoites are produced within the oocyst, located on the outside wall of the mosquito midgut, and migrate after release from the oocysts to the salivary glands where they are stored as mature infectious forms. Comparison of the proteomes of sporozoites derived from either the oocyst or from the salivary gland reveals remarkable differences in the protein content of these stages despite their similar morphology. The changes in protein content reflect the very specific preparations the sporozoites make in order to establish an infection of the liver. Analysis of the function of several previously uncharacterized, conserved proteins revealed proteins essential for sporozoite development at distinct points of their maturation.