The genome of the protist parasite Entamoeba histolytica

Journal name:
Nature
Volume:
433,
Pages:
865–868
Date published:
DOI:
doi:10.1038/nature03291
Received
Accepted

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries1. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.

At a glance

Figures

  1. Predicted metabolism of E. histolytica based on analysis of the genome sequence data.
    Figure 1: Predicted metabolism of E. histolytica based on analysis of the genome sequence data.

    Arrows indicate enzyme reactions. Glycolysis and fermentation are the major energy generation pathways. Green arrows represent enzymes encoded by genes that are among the 96 candidates for LGT into the E. histolytica genome. Broken arrows indicate enzymes for which no gene could be identified using searches of the genome data, although the activity is likely to be present. The yellow arrow points to the source of electrons for activation of metronidazole, the major drug for treatment of amoebic liver abscess. DK, pyruvate phosphate dikinase; GlcNAc, N-acetylglucosamine; GPI, glycosylphosphatidylinositol; K, pyruvate kinase; LCFA, long-chain fatty acid; PAPS, phosphoadenosine phosphosulphate; PEP, phosphoenolpyruvate; PP, pyrophosphate; PRPP, phosphoribosyl pyrophosphate; VLCFA, very-long-chain fatty acid.

  2. Predicted signal transduction mechanisms of E. histolytica based on analysis of the genome sequence data.
    Figure 2: Predicted signal transduction mechanisms of E. histolytica based on analysis of the genome sequence data.

    E. histolytica possesses three types of receptor serine/threonine kinases: one group has CXXC repeats in the extracellular domain; a second has CXC repeats; and a third has non-cysteine rich (NCR) repeats. E. histolytica has cytosolic tyrosine kinases (TyrK), but not receptor tyrosine kinases. Some serine/threonine phosphatases (S/TP) have an attached LRR domain. CaBP, calcium-binding protein; DAG, diacylglycerol; G, G protein; GAP, GTPase-activating protein; GEF, guanine nucleotide exchange factor; IP3, inositol-1,4,5-trisphosphate; PI(3)K, phosphatidylinositol-3-OH kinase; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-3,4,5-trisphosphate; PKC, protein kinase C; PLC, phospholipase C; PTEN, phosphatase and tensin homologue; TyrP, tyrosine phosphatase; 7TM receptors, seven-transmembrane receptors.

  3. Predicted pathways for oxidative and nitrosative stress resistance in E. histolytica.
    Figure 3: Predicted pathways for oxidative and nitrosative stress resistance in E. histolytica.

    Enzymes boxed and shaded have previously only been identified in anaerobic prokaryotes and amitochondrial protists. a, Superoxide is detoxified by an iron-containing superoxide dismutase (Fe-SOD). Molecular oxygen is reduced to hydrogen peroxide by the NADPH-flavin oxidoreductase (p34), which also transfers electrons to peroxiredoxin (p29). Rubrerythrin (Rbr) is predicted to convert hydrogen peroxide to water, although the source of electrons for rubrerythrin in E. histolytica is unknown. b, A-type flavoproteins (FprA) detoxify nitric oxide to nitrous oxide. FprA receives electrons from flavoprotein A reductase (Far).

Author information

Affiliations

  1. TIGR, 9712 Medical Center Drive, Rockville, Maryland 20850, USA

    • Brendan Loftus,
    • Iain Anderson,
    • Paolo Amedeo,
    • Paola Roncaglia,
    • Bernard Suh,
    • Mihai Pop,
    • Zheng Wang,
    • Najib M. El-Sayed &
    • Claire M. Fraser
  2. The Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK

    • Rob Davies,
    • Matt Berriman,
    • Tracey Chillingworth,
    • Carol Churcher,
    • Zahra Hance,
    • Barbara Harris,
    • David Harris,
    • Kay Jagels,
    • Sharon Moule,
    • Karen Mungall,
    • Doug Ormond,
    • Rob Squares,
    • Sally Whitehead,
    • Michael A. Quail,
    • Ester Rabbinowitsch,
    • Halina Norbertczak,
    • Claire Price,
    • Bart Barrell &
    • Neil Hall
  3. School of Biology, University of Newcastle, King George VI Building, Newcastle upon Tyne NE1 7RU, UK

    • U. Cecilia M. Alsmark,
    • Robert P. Hirt &
    • T. Martin Embley
  4. Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA

    • John Samuelson
  5. Departments of Internal Medicine & Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA

    • Barbara J. Mann,
    • Carol Gilchrist,
    • Suzanne E. Stroup &
    • William A. Petri Jr
  6. Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan

    • Tomo Nozaki
  7. Division of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria

    • Michael Duchene &
    • Margit Hofer
  8. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

    • John Ackers &
    • C. Graham Clark
  9. Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany

    • Egbert Tannich,
    • Iris Bruchhaus &
    • Ute Willhoeft
  10. Zoological Institute, University of Kiel, Olshausenstr. 40, 24098 Kiel, Germany

    • Matthias Leippe
  11. School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India

    • Alok Bhattacharya &
    • Sudha Bhattacharya
  12. Unite de Biologie Cellulaire du Parasitisme, INSERM U389, Institut Pasteur 28, rue du Dr Roux 75724, Paris Cedex 15, France

    • Nancy Guillén &
    • Christian Weber
  13. Department of Biochemistry, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata 700054, India

    • Anuradha Lohia &
    • Chandrama Mukherjee
  14. Department of Zoology, The Natural History Museum, Cromwell Road, London SW7 5BD, UK

    • Peter G. Foster
  15. Center for Biological Sequence Analysis, Technical University of Denmark, Building 208, DK-2800 Lyngby, Denmark

    • Thomas Sicheritz-Ponten
  16. Departments of Internal Medicine, Microbiology, and Immunology, Stanford University School of Medicine, Stanford, California 94305-5107, USA

    • Upinder Singh
  17. Present address: TIGR, 9712 Medical Center Drive, Rockville, Maryland 20850, USA

    • Neil Hall

Competing financial interests

The authors declare no competing financial interests.

The authors declare that they have no competing financial interests.

Corresponding author

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Author details

Supplementary information

Word documents

  1. Supplementary Data (217K)

    This file contains a table with 96 candidate LGT genes, a pie chart with functional categorization of LGT genes and a list of .pdf files containing phylogenetic trees for each candidate.

Excel files

  1. Supplementary Notes (57K)

    This file contains the GenBank accessions.

Zip files

  1. Supplementary Figures (1.4K)

    This zipped file contains pdf files of phylogenetic trees for 96 E. histolytica genes.

Additional data