Disruption of the Plasmodium falciparum liver-stage antigen-1 locus causes a differentiation defect in late liver-stage parasites
Version of Record online: 24 JUN 2011
© 2011 Blackwell Publishing Ltd
Volume 13, Issue 8, pages 1250–1260, August 2011
How to Cite
Mikolajczak, S. A., Sacci, Jr, J. B., De La Vega, P., Camargo, N., VanBuskirk, K., Krzych, U., Cao, J., Jacobs-Lorena, M., Cowman, A. F. and 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: 1250–1260. doi: 10.1111/j.1462-5822.2011.01617.x
- Issue online: 18 JUL 2011
- Version of Record online: 24 JUN 2011
- Accepted manuscript online: 13 MAY 2011 07:37AM EST
- Received 14 December, 2010; revised 4 April, 2011; accepted 23 April, 2011.
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.