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Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes

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Abstract

Malaria parasites undergo a sporogonic cycle in the mosquito vector. Sporozoites, the form of the parasite injected into the host during a bloodmeal, develop inside oocysts in the insect midgut, then migrate to and eventually invade the salivary glands. The circumsporozoite protein (CS), one of the major proteins synthesized by salivary gland sporozoites1, is a surface-associated molecule which is important in sporozoite infectivity to the host2. Here, by gene targeting, we created Plasmodium berghei lines in which the single-copy CS gene was disrupted. The CS( − ) and wild-type parasites produced similar numbers of oocysts of comparable size in the mosquito midgut. In the CS( − ) oocysts, however, sporozoite formation was profoundly inhibited. CS therefore appears to have a pleiotropic role and to be vital for malaria parasites in both the vector and the host: in mosquitoes, CS is essential for sporozoite development within oocysts, and in the vertebrate host it promotes sporozoite attachment to hepatocytes3–7.

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Authors and Affiliations

  1. Michael Heidelberger Division of Immunology, Department of Pathology, Kaplan Cancer Center, New York University Medical Center, New York, New York, 10016, USA

    Robert Ménard, Ali A. Sultan & Victor Nussenzweig

  2. Department of Medical and Molecular Parasitology, New York

    Robert Ménard, Claudio Cortes, Rita Altszuler & Ruth S. Nussenzweig

  3. University Medical Center, New York, New York, 10016, USA

    Claudio Cortes, Rita Altszuler & Ruth S. Nussenzweig

  4. Department of Parasitology, University of Leiden, 2300 RC, Leiden, The Netherlands

    Melissa R. van Dijk, Chris J. Janse & Andrew P. Waters

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  1. Robert Ménard
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  2. Ali A. Sultan
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  3. Claudio Cortes
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  4. Rita Altszuler
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  5. Melissa R. van Dijk
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  6. Chris J. Janse
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  7. Andrew P. Waters
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  8. Ruth S. Nussenzweig
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Ménard, R., Sultan, A., Cortes, C. et al. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature 385, 336–340 (1997). https://doi.org/10.1038/385336a0

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  • DOI: https://doi.org/10.1038/385336a0

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