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Plasmodium sporozoite phospholipid scramblase interacts with mammalian carbamoyl-phosphate synthetase 1 to infect hepatocytes

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  • Sung-Jae Cha

    (Department of Molecular Microbiology and Immunology and Malaria Research Institute)

  • Min-Sik Kim

    (Daegu Gyeongbuk Institute of Science and Technology (DGIST))

  • Chan Hyun Na

    (Johns Hopkins University)

  • Marcelo Jacobs-Lorena

    (Department of Molecular Microbiology and Immunology and Malaria Research Institute)

Abstract

After inoculation by the bite of an infected mosquito, Plasmodium sporozoites enter the blood stream and infect the liver, where each infected cell produces thousands of merozoites. These in turn, infect red blood cells and cause malaria symptoms. To initiate a productive infection, sporozoites must exit the circulation by traversing the blood lining of the liver vessels after which they infect hepatocytes with unique specificity. We screened a phage display library for peptides that structurally mimic (mimotope) a sporozoite ligand for hepatocyte recognition. We identified HP1 (hepatocyte-binding peptide 1) that mimics a ~50 kDa sporozoite ligand (identified as phospholipid scramblase). Further, we show that HP1 interacts with a ~160 kDa hepatocyte membrane putative receptor (identified as carbamoyl-phosphate synthetase 1). Importantly, immunization of mice with the HP1 peptide partially protects them from infection by the rodent parasite P. berghei. Moreover, an antibody to the HP1 mimotope inhibits human parasite P. falciparum infection of human hepatocytes in culture. The sporozoite ligand for hepatocyte invasion is a potential novel pre-erythrocytic vaccine candidate.

Suggested Citation

  • Sung-Jae Cha & Min-Sik Kim & Chan Hyun Na & Marcelo Jacobs-Lorena, 2021. "Plasmodium sporozoite phospholipid scramblase interacts with mammalian carbamoyl-phosphate synthetase 1 to infect hepatocytes," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27109-7
    DOI: 10.1038/s41467-021-27109-7
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    References listed on IDEAS

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    1. Ute Frevert & Sabine Engelmann & Sergine Zougbédé & Jörg Stange & Bruce Ng & Kai Matuschewski & Leonard Liebes & Herman Yee, 2005. "Intravital Observation of Plasmodium berghei Sporozoite Infection of the Liver," PLOS Biology, Public Library of Science, vol. 3(6), pages 1-1, May.
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