Malaria Parasites Lacking Eef1a Have a Normal S/M Phase Yet Grow More Slowly Due to a Longer G1 Phase

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.