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| The EMBO Journal
(1999) 18, 6221–6227, doi:10.1093/emboj/18.22.6221 |
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| CTRP is essential for mosquito infection by malaria ookinetes |
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| Johannes T. Dessens1, 3, Annette L. Beetsma1, 3, George Dimopoulos2, Kai Wengelnik1, Andrea Crisanti1, Fotis C. Kafatos2 and Robert E. Sinden1 |
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1 Infection and Immunity Section, Department of Biology, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Building, Imperial College Road, London SW7 2AZ, UK 2 European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany 3 J.T.Dessens and A.L.Beetsma contributed equally to this work To whom correspondence should be addressed Robert E. Sinden, r.sinden@ic.ac.uk Received 10 August 1999; Revised 5 October 1999; Accepted 6 October 1999. |
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| Abstract |
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| The malaria parasite suffers severe population losses as it passes through its mosquito vector. Contributing factors are the essential but highly constrained developmental transitions that the parasite undergoes in the mosquito midgut, combined with the invasion of the midgut epithelium by the malaria ookinete (recently described as a principal elicitor of the innate immune response in the Plasmodium-infected insect). Little is known about the molecular organization of these midgut-stage parasites and their critical interactions with the blood meal and the mosquito vector. Elucidation of these molecules and interactions will open up new avenues for chemotherapeutic and immunological attack of parasite development. Here, using the rodent malaria parasite Plasmodium berghei, we identify and characterize the first microneme protein of the ookinete: circumsporozoite- and TRAP-related protein (CTRP). We show that transgenic parasites in which the CTRP gene is disrupted form ookinetes that have reduced motility, fail to invade the midgut epithelium, do not trigger the mosquito immune response, and do not develop further into oocysts. Thus, CTRP is the first molecule shown to be essential for ookinete infectivity and, consequently, mosquito transmission of malaria. |
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| Keywords: microneme, mosquito, Plasmodium berghei, transgenic parasite |
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