[Genetic approach to the study of the sporogonic cycle in Plasmodium]

Abstract

The development of transformation and mutagenesis techniques of the two species of Plasmodium most studied--Plasmodium falciparum (human parasite) and Plasmodium berghei (rodent parasite)--opens new perspectives for the molecular study on the parasite sporogonic cycle in the insect vector. The parasite's stages that can be genetically transformed (the asexual erythrocytic stages) and gametocytes. The function of proteins coded by genes present in single copy in the genome can thus be studied after only one recombination. Furthermore, most of the genes expressed during the sporogonic cycle are not during the erythrocytic stages, which makes possible the isolation of the erythrocytic cycles of parasites with a mutation in a gene which is essential to the development of the sporogonic cycle. Finally, the Plasmodium berghei model is particularly advantageous in that the entire cycle of this species of Plasmodium can be easily maintained in the laboratory. The species also appears to be easier to manipulate genetically than Plasmodium falciparum. Let us take the example of two surface proteins of Plasmodium sporozoites: the circumsporozoite proteins (CS) and the thrombospondin-related anonymous protein (TRAP). Both of these proteins have already been characterized in detail. Each of them possesses motives present in numerous protein of cell-cell or extracellular cell-matrice adhesion. The selective destruction of both genes has shown that both proteins also play a role in the development of the parasite within the mosquito. The CS protein is essential to the formation of sporozoites in the mosquito's intestinal oocysts, whereas the TRAP protein is essential for the sporozoites to have the power to invade the secreting cells of the mosquito's salivary glands as well as the host's hepatocytes. Using the mutagenous system for P. berghei should thus help elucidate the function of the important products expressed by the parasite during its development cycle in the vector mosquito as well as analyse the structure-function relationship of these products. It is possible that the molecular dissection of the parasite-mosquito interaction will lead to new approaches in the prevention of parasite transmission.