title: Malaria parasites lacking eef1a have a normal S/M phase yet grow more slowly due to a longer G1 phase.
abstract: Eukaryotic elongation factor 1A (eEF1A) plays a central role in protein synthesis, cell growth and morphology. Malaria parasites possess two identical genes encoding eEF1A (eef1aa and eef1ab). Using pbeef1a-Plasmodium berghei mutants that lack an eEF1a gene, we demonstrate that the level of eEF1A production affects the proliferation of blood stages and parasite fitness. Pbeef1a- parasites can complete the vertebrate and mosquito phases of the life cycle, but the growth phase of the asexual blood stages is extended by up to 20%. Analysis of the cell cycle by flow cytometry as well as transcriptional analyses revealed that the duration of the S and M phases and the number of daughter cells produced were not detectably affected, but that the G1 phase is elongated. Thus, as in budding yeast, a growth threshold must be achieved by blood-stage Plasmodium parasites to permit transition from G1 into S/M phase. Initial analyses indicate that transcriptional events associated with gametocyte development were not remarkably retarded. Insight into protein synthesis and its influence on cell proliferation might be used to generate slow-growing (attenuated) parasites.
authors.affiliation: Malaria Group, Department of Parasitology, Leiden University Medical Centre (LUMC), PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Alireza
authors.initials: A
authors.lastname: Haghparast
authors.forename: Márcia A
authors.initials: MA
authors.lastname: Sperança
authors.forename: Jai
authors.initials: J
authors.lastname: Ramesar
authors.forename: Hans
authors.initials: H
authors.lastname: Kroeze
authors.forename: Hernando A
authors.initials: HA
authors.lastname: del Portillo
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Waters
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D016193:G1 Phase; D018507:Gene Expression Regulation, Developmental; D005818:Genetic Engineering / Q000379:methods; D008288:Malaria / Q000469:parasitology; D051379:Mice; D008938:Mitosis; D009154:Mutation; D018512:Parasitemia / Q000469:parasitology; D020648:Peptide Elongation Factor 1 / Q000235:genetics*; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development*; D016196:S Phase; D013997:Time Factors
chemical_list: D020648:Peptide Elongation Factor 1