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Developmental transition of Plasmodium sporozoites into liver-stage forms is regulated by the RNA binding protein Pumilio 2

  • Carina SS Gomes-Santos1, 2,
  • J Anneke M Braks3,
  • Miguel Prudêncio1,
  • Céline K Carret4,
  • Ana Rita Gomes4,
  • Arnab Pain5,
  • Theresa Feltwell5,
  • Shahid M Khan3,
  • Andrew P Waters6,
  • Chris J Janse3,
  • Gunnar R Mair4 and
  • Maria M Mota1
Malaria Journal20109(Suppl 2):P13

Published: 20 October 2010


PlasmodiumMammalian HostCell Fate DecisionPlasmodium BergheiUnicellular Eukaryote

Developmental and cell fate decisions in many organisms are frequently made on a post-transcriptional level that involves RNA binding proteins and mechanisms of translational repression and regulation of translation of key mRNAs. In the unicellular eukaryote Plasmodium, one of the most dramatic life-cycle dependent changes in cell morphology and function occurs during transmission from the mosquito to the human host. In the mosquito salivary glands Plasmodium sporozoites remain slender, motile and infectious for several days/weeks. At this stage, Plasmodium parasites are on stand-by, awaiting injection onto the mammalian host. Immedietaly fter transmission and liver cell invasion, a remarkable differentiation process is initiated. During this process, each parasite rapidly transforms into a round, stationary exo-erythrocytic form (EEF) that expands into thousands of infectious merozoites to be released into the blood stream. Here we reveal a Plasmodium homolog of the RNA binding protein Pumilio as a key regulator of the sporozoite to EEF transition. In the absence of Pumilio-2 (Puf2), Plasmodium berghei sporozoites initiate early stage EEF development inside mosquito salivary glands, in the absence of the appropriate environmental cues. Mutant salivary gland sporozoites present reduced motility but also significantly reduced ability to invade and infect their mammalian host cells, both in vitro and in vivo. Global expression profiling confirmed that transgenic parasites exhibit genome-wide transcriptional adaptations that are typical for Plasmodium intra-hepatic development. Our data, demonstrates that Puf2 is a key player in the developmental control involved in the transition between sporozoite and EEF, implying that transformation of salivary gland-resident sporozoites into early liver stage parasites is in fact prevented by a post-translational mechanism.

Authors’ Affiliations

Malaria Unit, Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisboa, Portugal
PhD Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Laboratory for Parasitology, Leiden University Medical Centre, Leiden, The Netherlands
Unidade de Parasitologia Molecular, Instituto de Medicina Molecular, Lisboa, Portugal
Pathogen Genetics Group, Wellcome Trust Sanger Institute, Cambridge, UK
Division of Infection and Immunity, Institute of Biomedical Life Sciences & Wellcome Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK


© Prudêncio et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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