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Infection and Immunity, July 2005, p. 3912-3922, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.3912-3922.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Plasmodium falciparum Merozoite Surface Protein 8 Is a Ring-Stage Membrane Protein That Localizes to the Parasitophorous Vacuole of Infected Erythrocytes

Damien R. Drew, Paul R. Sanders, and Brendan S. Crabb*

The Walter and Eliza Hall Institute for Medical Research, Parkville, Australia, 3050

Received 17 January 2005/ Returned for modification 15 February 2005/ Accepted 28 February 2005

To date, the following seven glycosylphosphatidylinositol (GPI)-anchored merozoite antigens have been described in Plasmodium falciparum: merozoite-associated surface protein 1 (MSP-1), MSP-2, MSP-4, MSP-5, MSP-8, MSP-10, and the rhoptry-associated membrane antigen. Of these, MSP-1, MSP-8, and MSP-10 possess a double epidermal growth factor (EGF)-like domain at the C terminus, and these modules are considered potential targets of protective immunity. In this study, we found that surprisingly, P. falciparum MSP-8 is transcribed and translated in the ring stage and is absent from the surface of merozoites. MSP-8 is the only GPI-anchored protein known to be expressed at this time. It is synthesized as a mature 80-kDa protein which is rapidly processed to a C-terminal 17-kDa species that contains the double EGF module. As determined by a combination of immunofluorescence and membrane purification approaches, it appears likely that MSP-8 initially localizes to the parasite plasma membrane in the ring stage. Although the C-terminal 17-kDa fragment is present in more mature stages, at these times it is found in the food vacuole. We successfully disrupted the MSP-8 gene in P. falciparum, a process that validated the specificity of the antibodies used in this study and also demonstrated that MSP-8 does not play a role essential to maintenance of the erythrocyte cycle. This finding, together with the observation that MSP-8 is exclusively intracellular, casts doubt over the viability of this antigen as a vaccine. However, it is still possible that MSP-8 is involved in an early parasitophorous vacuole function that is significant for pathogenesis in the human host.

* Corresponding author. Mailing address: The Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3050, Australia. Phone: 61 3 9345 2555. Fax: 61 3 9347 0852. E-mail: crabb{at}wehi.edu.au.

Editor: W. A. Petri, Jr.

Infection and Immunity, July 2005, p. 3912-3922, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.3912-3922.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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