Critical roles of glycosylphosphatidylinositol for <i>Trypanosoma brucei</i>

  • Kisaburo Nagamune
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Tomoyoshi Nozaki
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Yusuke Maeda
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Kazuhito Ohishi
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Toshihide Fukuma
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Tatsuru Hara
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Ralph T. Schwarz
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Christine Sütterlin
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Reto Brun
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Howard Riezman
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...
  • Taroh Kinoshita
    Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan; Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; Medical Center of Hygiene and Medical Microbiology, University of Marburg, Robert Koch Strasse 17, Postfach 2360, Marburg D...

抄録

<jats:p> <jats:italic>Trypanosoma brucei</jats:italic> , the protozoan parasite responsible for sleeping sickness, evades the immune response of mammalian hosts and digestion in the gut of the insect vector by means of its coat proteins tethered to the cell surface via glycosylphosphatidylinositol (GPI) anchors. To evaluate the importance of GPI for parasite survival, we cloned and disrupted a trypanosomal gene, <jats:italic>TbGPI10</jats:italic> , involved in biosynthesis of GPI. <jats:italic>TbGPI10</jats:italic> encodes a protein of 558 amino acids having 25% and 23% sequence identity to human PIG-B and <jats:italic>Saccharomyces cerevisiae</jats:italic> Gpi10p, respectively. <jats:italic>TbGPI10</jats:italic> restored biosynthesis of GPI in a mouse mutant cell line defective in mouse <jats:italic>Pig-b</jats:italic> gene. <jats:italic>TbGPI10</jats:italic> also rescued the inviability of <jats:italic>GPI10</jats:italic> -disrupted <jats:italic>S. cerevisiae</jats:italic> , indicating that <jats:italic>TbGPI10</jats:italic> is the orthologue of <jats:italic>PIG-B</jats:italic> / <jats:italic>GPI10</jats:italic> that is involved in the transfer of the third mannose to GPI. The bloodstream form of <jats:italic>T. brucei</jats:italic> could not lose <jats:italic>TbGPI10</jats:italic> ; therefore, GPI synthesis is essential for growth of mammalian stage parasites. Procyclic form cells (insect stage parasites) lacking the surface coat proteins because of disruption of <jats:italic>TbGPI10</jats:italic> are viable and grow slower than normal, provided that they are cultured in nonadherent flasks. In regular flasks, they adhered to the plastic surface and died. Infectivity to tsetse flies is partially impaired, particularly in the early stage. Therefore, parasitespecific inhibition of GPI biosynthesis should be an effective chemotherapy target against African trypanosomiasis. </jats:p>

収録刊行物

被引用文献 (11)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ