Disruption of the Plasmodium falciparum liver-stage antigen-1 locus causes a differentiation defect in late liver-stage parasites.
Disruption of the Plasmodium falciparum liver-stage antigen-1 locus causes a differentiation defect in late liver-stage parasites.
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DOI：
10.1111/j.1462-5822.2011.01617.x
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发表时间：
2011-08
影响因子：
3.4
通讯作者：
Kappe SH
中科院分区：
文献类型：
--
作者：
Mikolajczak SA;Sacci JB Jr;De La Vega P;Camargo N;VanBuskirk K;Krzych U;Cao J;Jacobs-Lorena M;Cowman AF;Kappe SH
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.
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影响因子：
64.8
作者：
HILL, AVS;ELVIN, J;WHITTLE, HC
通讯作者：
WHITTLE, HC
影响因子：
5.5
作者：
Cummings, James F.;Spring, Michele D.;Heppner, D. Gray, Jr.
通讯作者：
Heppner, D. Gray, Jr.
DOI：
10.4269/ajtmh.2002.66.372
发表时间：
2002-04-01
影响因子：
3.3
作者：
John, CC;Ouma, JH;King, CL
通讯作者：
King, CL
影响因子：
3
作者：
Nicoll, William S.;Sacci, John B.;Lanar, David E.
通讯作者：
Lanar, David E.
影响因子：
10.5
作者：
Aly AS;Vaughan AM;Kappe SH
通讯作者：
Kappe SH