Disruption of the Plasmodium falciparum liver-stage antigen-1 locus causes a differentiation defect in late liver-stage parasites
- Author(s)
- Mikolajczak, SA; Sacci, JB; De La Vega, P; Camargo, N; VanBuskirk, K; Krzych, U; Cao, J; Jacobs-Lorena, M; Cowman, AF; Kappe, SHI;
- Details
- Publication Year 2011-08,Volume 13,Issue #8,Page 1250-1260
- Journal Title
- CELLULAR MICROBIOLOGY
- Publication Type
- Journal Article
- 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 similar to 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.
- Publisher
- WILEY-BLACKWELL
- Keywords
- CHIMERIC HUMAN LIVERS; MALARIA PARASITES; SPOROZOITES; INFECTION; ESTABLISHMENT; TRANSMISSION; HEPATOCYTES; PROTECTION; RESPONSES; PROTEINS
- Publisher's Version
- https://doi.org/10.1111/j.1462-5822.2011.01617.x
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2011-08-01 12:00:00