title: Molecular factors that are associated with early developmental arrest of intraerythrocytic Plasmodium 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.
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, 23-1 Toyama 1-chome, Shinjuku-ku, Tokyo 162-8640, Japan. asahih@nih.go.jp
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asahi
authors.forename: Mohammed Essa Marghany
authors.initials: ME
authors.lastname: Tolba
authors.forename: Masanobu
authors.initials: M
authors.lastname: Tanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohmae
mesh_terms: D000217:Acyltransferases / Q000378:metabolism; D000953:Antigens, Protozoan / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology*; D005227:Fatty Acids / Q000378:metabolism*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008288:Malaria / Q000469:parasitology*; D052940:Merozoites / Q000254:growth & development; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D053058:Trophozoites / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D005227:Fatty Acids; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C057495:serine repeat antigen, Plasmodium; D003300:Copper; D000217:Acyltransferases