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The Mitochondrial Genome and a 60-kb Nuclear DNA Segment from Naegleria fowleri, the Causative Agent of Primary Amoebic Meningoencephalitis

Authors

  • Emily K. Herman,

    1. Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
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    • These authors contributed equally to this work.
  • Alexander L. Greninger,

    1. UCSF-Abbott Viral Diagnostics and Discovery Center, University of California San Francisco, San Francisco, California, USA
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    • These authors contributed equally to this work.
  • Govinda S. Visvesvara,

    1. Division of Foodborne, Waterborne and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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  • Francine Marciano-Cabral,

    1. Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
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  • Joel B. Dacks,

    Corresponding author
    • Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
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  • Charles Y. Chiu

    Corresponding author
    1. UCSF-Abbott Viral Diagnostics and Discovery Center, University of California San Francisco, San Francisco, California, USA
    2. Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, USA
    3. Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA
    • Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
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Correspondence

J.B. Dacks, Department of Cell Biology, University of Alberta, 5-31 Medical Sciences Building, Edmonton, Canada T6G 2H7 Telephone number: +780-248-1493; Fax number: 780-492-0450; e-mail: dacks@ualberta.ca and C.Y. Chiu, Departments of Laboratory Medicine and Medicine (Infectious Diseases), UCSF School of Medicine, 185 Berry Street, UCSF China Basin, San Francisco, California 94143-0134 Telephone number: +415-514-8219; Fax number: 415-889-6441; e-mail: charles.chiu@ucsf.edu

Abstract

Naegleria fowleri is a unicellular eukaryote causing primary amoebic meningoencephalitis, a neuropathic disease killing 99% of those infected, usually within 7–14 days. Naegleria fowleri is found globally in regions including the US and Australia. The genome of the related nonpathogenic species Naegleria gruberi has been sequenced, but the genetic basis for N. fowleri pathogenicity is unclear. To generate such insight, we sequenced and assembled the mitochondrial genome and a 60-kb segment of nuclear genome from N. fowleri. The mitochondrial genome is highly similar to its counterpart in N. gruberi in gene complement and organization, while distinct lack of synteny is observed for the nuclear segments. Even in this short (60-kb) segment, we identified examples of potential factors for pathogenesis, including ten novel N. fowleri-specific genes. We also identified a homolog of cathepsin B; proteases proposed to be involved in the pathogenesis of diverse eukaryotic pathogens, including N. fowleri. Finally, we demonstrate a likely case of horizontal gene transfer between N. fowleri and two unrelated amoebae, one of which causes granulomatous amoebic encephalitis. This initial look into the N. fowleri nuclear genome has revealed several examples of potential pathogenesis factors, improving our understanding of a neglected pathogen of increasing global importance.

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