Disruption of Plasmodium berghei merozoite surface protein 7 gene modulates parasite growth in vivo.

Merozoite invasion of red blood cells is crucial to the development of the parasite that causes malaria. Merozoite surface proteins (MSPs) mediate the first interaction between parasite and erythrocyte. In Plasmodium falciparum, they include a complex of products from at least 3 genes (msp1, msp6, and msp7), one of which, msp7, is part of a gene family containing 3 and 6 adjacent members in Plasmodium yoelii and Plasmodium falciparum, respectively. We have identified and disrupted msp7 in the Plasmodium berghei gene family. The protein is expressed in schizonts and colocalizes with MSP1. The synthesis and processing of MSP1 was unaffected in the parasite with the disrupted gene (MSP7ko). Disruption of msp7 was not lethal but affected blood-stage parasite growth. MSP7ko parasites initially grew more slowly than wild-type parasites. However, when reticulocytes were prevalent, the rate of increase in parasitemia was similar, suggesting that MSP7ko parasites prefer to invade and grow within reticulocytes.

[1]  M. Grainger,et al.  N-terminal amino acid sequence of the Plasmodium falciparum merozoite surface protein-1 polypeptides. , 1994, Molecular and biochemical parasitology.

[2]  J. McBride,et al.  Fragments of the polymorphic Mr 185,000 glycoprotein from the surface of isolated Plasmodium falciparum merozoites form an antigenic complex. , 1987, Molecular and biochemical parasitology.

[3]  S. Howell,et al.  The 22 kDa component of the protein complex on the surface of Plasmodium falciparum merozoites is derived from a larger precursor, merozoite surface protein 7. , 2001, Molecular and biochemical parasitology.

[4]  A. Vaidya,et al.  A Multigene Family That Interacts with the Amino Terminus of Plasmodium MSP-1 Identified Using the Yeast Two-Hybrid System , 2002, Eukaryotic Cell.

[5]  S. Hoffman,et al.  Preventing merozoite invasion of erythrocytes. , 1996 .

[6]  B. Mons.  Preferential invasion of malarial merozoites into young red blood cells. , 1990, Blood cells.

[7]  A. Holder,et al.  Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1. , 1992, Molecular and biochemical parasitology.

[8]  A. Holder.  The precursor to major merozoite surface antigens: structure and role in immunity. , 1988, Progress in allergy.

[9]  A. Cowman,et al.  The Plasmodium falciparum Genome-- a Blueprint for Erythrocyte Invasion , 2002, Science.

[10]  A. Holder,et al.  Function of Region I and II Adhesive Motifs ofPlasmodium falciparum Circumsporozoite Protein in Sporozoite Motility and Infectivity* , 2002, The Journal of Biological Chemistry.

[11]  A. Holder,et al.  Processing of the precursor to the major merozoite surface antigens of Plasmodium falciparum , 1987, Parasitology.

[12]  A. Thomas,et al.  Transfection of malaria parasites. , 1997, Methods.

[13]  W. Taylor,et al.  The merozoite surface protein 6 gene codes for a 36 kDa protein associated with the Plasmodium falciparum merozoite surface protein-1 complex. , 2001, Molecular and biochemical parasitology.

[14]  K. J. Ott.  Influence of reticulocytosis on the course of infection of Plasmodium chabaudi and P. berghei. , 1968, The Journal of protozoology.

[15]  A. Holder,et al.  A 22 kDa protein associated with the Plasmodium falciparum merozoite surface protein-1 complex. , 1996, Molecular and biochemical parasitology.

[16]  T. Triglia,et al.  Functional analysis of Plasmodium falciparum merozoite antigens: implications for erythrocyte invasion and vaccine development. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[17]  A. Holder,et al.  Plasmodium yoelii: brefeldin A-sensitive processing of proteins targeted to the rhoptries. , 1994, Experimental parasitology.

[18]  A. Holder,et al.  A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion- inhibiting antibodies , 1990, The Journal of experimental medicine.