Disruption of the plasmodium falciparum liver-stage antigen-1 locus causes a differentiation defect in late liver-stage parasites

Sebastian A. Mikolajczak, John B. Sacci, Patricia De La Vega, Nelly Camargo, Kelly Vanbuskirk, Urszula Krzych, Jun Cao, Marcelo Jacobs-Lorena, Alan F. Cowman, Stefan H.I. Kappe

Research output: Contribution to journalArticle

Abstract

The malaria parasite Plasmodium falciparum infects humans and first targets the liver where liver-stage parasites undergo pre-erythrocytic replication. Liver-stage antigen-1 (LSA-1) is currently the only identified P. falciparum protein for which expression is restricted to liver stages. Yet, the importance of LSA-1 for liver-stage parasite development remains unknown. Here we deleted LSA-1 in the NF54 strain of P. falciparum and analysed the lsa-1- parasites throughout their life cycle. lsa-1- sporozoites had normal gliding motility and invasion into hepatocytes. Six days after infection of a hepatocytic cell line, lsa-1- parasites exhibited a moderate phenotype with an∼50% reduction of late liver-stage forms when compared with wild type. Strikingly, lsa-1- parasites growing in SCID/Alb-uPA mice with humanized livers showed a severe defect in late liver-stage differentiation and exo-erythrocytic merozoite formation 7 days after infection, a time point when wild-type parasites develop into mature merozoites. The lsa-1- parasites also showed aberrant liver-stage expression of key parasite proteins apical membrane antigen-1 and circumsporozoite protein. Our data show that LSA-1 plays a critical role during late liver-stage schizogony and is thus important in the parasite transition from the liver to blood. LSA-1 is the first P. falciparum protein identified to be required for this transitional stage of the parasite life cycle.

Original languageEnglish (US)
Pages (from-to)1250-1260
Number of pages11
JournalCellular microbiology
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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    Mikolajczak, S. A., Sacci, J. B., De La Vega, P., Camargo, N., Vanbuskirk, K., Krzych, U., Cao, J., Jacobs-Lorena, M., Cowman, A. F., & Kappe, S. H. I. (2011). Disruption of the plasmodium falciparum liver-stage antigen-1 locus causes a differentiation defect in late liver-stage parasites. Cellular microbiology, 13(8), 1250-1260. https://doi.org/10.1111/j.1462-5822.2011.01617.x