Molecular factors that are associated with early developmental arrest of intraerythrocyticPlasmodium falciparum

Abstract

Malaria continues to be a devastating disease. We investigated the factors that control intraerythrocytic development of the parasite Plasmodium falciparum by using a chemically defined medium (CDM) containing non-esterified fatty acid(s) (NEFA) and phospholipids with specific fatty acid moieties, to identify substances crucial for parasite development. Different NEFAs in the CDM played distinct roles by altering the development of the parasite at various stages, with effects ranging from complete growth to growth arrest at the ring stage. We used genome-wide transcriptome profiling to identify genes that were differentially expressed among the different developmental stages of the parasite, cultured in the presence of various NEFAs. We predicted 26 transcripts that were associated with the suppression of schizogony, of which 5 transcripts, including merozoite surface protein 2, a putative DEAD/DEAH box RNA helicase, serine repeat antigen 3, a putative copper channel, and palmitoyl acyltransferase, were particularly associated with blockage of trophozoite progression from the ring stage. Furthermore, the involvement of copper ions in developmental arrest was detected by copper-ion-chelating methods, implying a critical function of copper homeostasis in the early growth stage of the parasite. These results should help to elucidate the mechanisms behind the development of P. falciparum.