A Multidomain Adhesion Protein Family Expressed in Plasmodium falciparum Is Essential for Transmission to the Mosquito

Author:

Pradel Gabriele1,Hayton Karen2,Aravind L.3,Iyer Lakshminarayan M.3,Abrahamsen Mitchell S.4,Bonawitz Annemarie1,Mejia Cesar1,Templeton Thomas J.1

Affiliation:

1. Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021

2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases,

3. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892

4. Biomedical Genomics Center and Department of Veterinary Pathobiology, University of Minnesota, St. Paul, MN 55108

Abstract

The recent sequencing of several apicomplexan genomes has provided the opportunity to characterize novel antigens essential for the parasite life cycle that might lead to the development of new diagnostic and therapeutic markers. Here we have screened the Plasmodium falciparum genome sequence for genes encoding extracellular multidomain putative adhesive proteins. Three of these identified genes, named PfCCp1, PfCCp2, and PfCCp3, have multiple adhesive modules including a common Limulus coagulation factor C domain also found in two additional Plasmodium genes. Orthologues were identified in the Cryptosporidium parvum genome sequence, indicating an evolutionary conserved function. Transcript and protein expression analysis shows sexual stage–specific expression of PfCCp1, PfCCp2, and PfCCp3, and cellular localization studies revealed plasma membrane–associated expression in mature gametocytes. During gametogenesis, PfCCps are released and localize surrounding complexes of newly emerged microgametes and macrogametes. PfCCp expression markedly decreased after formation of zygotes. To begin to address PfCCp function, the PfCCp2 and PfCCp3 gene loci were disrupted by homologous recombination, resulting in parasites capable of forming oocyst sporozoites but blocked in the salivary gland transition. Our results describe members of a conserved apicomplexan protein family expressed in sexual stage Plasmodium parasites that may represent candidates for subunits of a transmission-blocking vaccine.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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