Infectious diseases continue to be a global health problem and are the cause of tremendous morbidity and mortality every year. Attempts to create effective and protective vaccines have been a high global health priority. New generation of vaccines based on modern cellular and molecular approaches have helped to create the valuable tools to combat such health problems. Identification of elements and components that are necessary for virulence and try to eliminate them from the genome is a step towards developing attenuated live parasite as vaccine. Cell division and proliferation during parasite invasion are prerequisites factors for virulence. Eukaryotic elongation factor 1A (eEF1A) plays a central role in protein synthesis, cell growth and morphology. Malaria parasite possesses 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 in malaria parasites might be used for drug discovery as well as generating slow growing parasites to study immunological intervention strategies involved in host-parasite interactions. Further attenuation of parasites through elongation of the cell cycle by affecting protein synthesis machinery might be used for testing the feasibility of the creation of attenuated live parasites as vaccine.

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