Malaria parasite evades mosquito immunity by glutaminyl cyclase–mediated posttranslational protein modification

DOI HANDLE Web Site PubMed Research Data 1 Citations 70 References
  • Surendra Kumar Kolli
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Alvaro Molina-Cruz
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852
  • Tamasa Araki
    Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan
  • Fiona J. A. Geurten
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Jai Ramesar
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Severine Chevalley-Maurel
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Hans J. Kroeze
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Sascha Bezemer
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Clarize de Korne
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Roxanne Withers
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852
  • Nadia Raytselis
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852
  • Angela F. El Hebieshy
    Oncode Institute, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands
  • Robbert Q. Kim
    Oncode Institute, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands
  • Matthew A. Child
    Department of Life Sciences, Imperial College London, London, SW7 2AZ, United Kingdom
  • Soichiro Kakuta
    Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo 113-8421, Japan
  • Hajime Hisaeda
    Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan
  • Hirotaka Kobayashi
    Department of Pathology, National Institute of Infectious Diseases, Shinjukuku, Tokyo 162-8640, Japan
  • Takeshi Annoura
    Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan
  • Paul J. Hensbergen
    Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Blandine M. Franke-Fayard
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands
  • Carolina Barillas-Mury
    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852
  • Ferenc A. Scheeren
    Department of Dermatology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands
  • Chris J. Janse
    Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands

Description

<jats:p> Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of <jats:italic>Plasmodium</jats:italic> QC. We show that sporozoites of QC-null mutants of rodent and human malaria parasites are recognized by the mosquito immune system and melanized when they reach the hemocoel. Detailed analyses of rodent malaria QC-null mutants showed that sporozoite numbers in salivary glands are reduced in mosquitoes infected with QC-null or QC catalytically dead mutants. This phenotype can be rescued by genetic complementation or by disrupting mosquito melanization or phagocytosis by hemocytes. Mutation of a single QC-target glutamine of the major sporozoite surface protein (circumsporozoite protein; CSP) of the rodent parasite <jats:italic>Plasmodium berghei</jats:italic> also results in melanization of sporozoites. These findings indicate that QC-mediated posttranslational modification of surface proteins underlies evasion of killing of sporozoites by the mosquito immune system. </jats:p>

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