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

Autor: Mikolajczak SA; Seattle Biomedical Research Institute, Seattle, WA 98109, USA., Sacci JB Jr, De La Vega P, Camargo N, VanBuskirk K, Krzych U, Cao J, Jacobs-Lorena M, Cowman AF, Kappe SH
Jazyk: angličtina
Zdroj: Cellular microbiology [Cell Microbiol] 2011 Aug; Vol. 13 (8), pp. 1250-60. Date of Electronic Publication: 2011 Jun 24.
DOI: 10.1111/j.1462-5822.2011.01617.x
Abstrakt: 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.
(© 2011 Blackwell Publishing Ltd.)
Databáze: MEDLINE
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