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.

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