1887

Abstract

Species in the genus are free-living amoebae of the soil and warm fresh water. Although around 30 species have been recognized, is the only one that causes primary amoebic meningoencephalitis (PAM) in humans. PAM is an acute and fast progressing disease affecting the central nervous system. Most of the patients die within 1–2 weeks of exposure to the infectious water source. The fact that causes such fast progressing and highly lethal infections has opened many questions regarding the relevant pathogenicity factors of the amoeba. In order to investigate the pathogenesis of under defined experimental conditions, we developed a novel high- versus low-pathogenicity model for this pathogen. We showed that the composition of the axenic growth media influenced growth behaviour and morphology, as well as cytotoxicity and pathogenicity of Trophozoites maintained in Nelson's medium were highly pathogenic for mice, demonstrated rapid proliferation, characteristic expression of surface membrane vesicles and a small cell diameter, and killed target mouse fibroblasts by both contact-dependent and -independent destruction. In contrast, cultured in PYNFH medium exhibited a low pathogenicity, slower growth, increased cell size and contact-dependent target cell destruction. However, cultivation of the amoeba in PYNFH medium supplemented with liver hydrolysate (LH) resulted in trophozoites that were highly pathogenic in mice, and demonstrated an intermediate proliferation rate , diminished cell diameter and contact-dependent target cell destruction. Thus, in this model, the presence of LH resulted in increased proliferation of trophozoites and enhanced pathogenicity of in mice. However, neither cytotoxicity mechanisms nor the presence of membrane vesicles on the surface correlated with the pathologic potential of the amoeba. This indicated that the pathogenicity of remains a complex interaction between as-yet-unidentified cellular mechanisms.

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2012-10-01
2019-10-23
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References

  1. Aldape K. , Huizinga H. , Bouvier J. , McKerrow J. . ( 1994; ). Naegleria fowleri: characterization of a secreted histolytic cysteine protease. . Exp Parasitol 78:, 230–241. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bradley S. G. , Toney D. M. , Zhang Y. , Marciano-Cabral F. . ( 1996; ). Dependence of growth, metabolic expression, and pathogenicity of Naegleria fowleri on exogenous porphyrins. . J Parasitol 82:, 763–768. [CrossRef] [PubMed]
    [Google Scholar]
  3. Brown T. . ( 1978; ). Observations by light microscopy on the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures. . J Med Microbiol 11:, 249–259. [CrossRef] [PubMed]
    [Google Scholar]
  4. Brown T. . ( 1979; ). Observations by immunofluorescence microscopy and electron microscopy on the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures. . J Med Microbiol 12:, 363–371. [CrossRef] [PubMed]
    [Google Scholar]
  5. Carter R. F. . ( 1970; ). Description of a Naegleria sp. isolated from two cases of primary amoebic meningo-encephalitis, and of the experimental pathological changes induced by it. . J Pathol 100:, 217–244. [CrossRef] [PubMed]
    [Google Scholar]
  6. De Jonckheere J. F. . ( 1980; ). Growth characteristics, cytopathic effect in cell culture, and virulence in mice of 36 type strains belonging to 19 different Acanthamoeba spp. . Appl Environ Microbiol 39:, 681–685.[PubMed]
    [Google Scholar]
  7. De Jonckheere J. F. . ( 2004; ). Molecular definition and the ubiquity of species in the genus Naegleria . . Protist 155:, 89–103. [CrossRef] [PubMed]
    [Google Scholar]
  8. de Jonckheere J. , Voorde H. . ( 1977; ). The distribution of Naegleria fowleri in man-made thermal waters. . Am J Trop Med Hyg 26:, 10–15.[PubMed]
    [Google Scholar]
  9. Fulford D. E. , Marciano-Cabral F. . ( 1986; ). Cytolytic activity of Naegleria fowleri cell-free extract. . J Protozool 33:, 498–502.[PubMed] [CrossRef]
    [Google Scholar]
  10. Gianinazzi C. , Schild M. , Müller N. , Leib S. L. , Simon F. , Nuñez S. , Joss P. , Gottstein B. . ( 2005; ). Organotypic slice cultures from rat brain tissue: a new approach for Naegleria fowleri CNS infection in vitro. . Parasitology 131:, 797–804. [CrossRef] [PubMed]
    [Google Scholar]
  11. Haggerty R. M. , John D. T. . ( 1978; ). Innate resistance of mice to experimental infection with Naegleria fowleri . . Infect Immun 20:, 73–77.[PubMed]
    [Google Scholar]
  12. Haight J. B. , John D. T. . ( 1980; ). Growth of Naegleria fowleri in several axenic media. . Folia Parasitol (Praha) 27:, 207–212.[PubMed]
    [Google Scholar]
  13. Han K. L. , Lee H. J. , Shin M. H. , Shin H. J. , Im K. I. , Park S. J. . ( 2004; ). The involvement of an integrin-like protein and protein kinase C in amoebic adhesion to fibronectin and amoebic cytotoxicity. . Parasitol Res 94:, 53–60. [CrossRef] [PubMed]
    [Google Scholar]
  14. Herbst R. , Ott C. , Jacobs T. , Marti T. , Marciano-Cabral F. , Leippe M. . ( 2002; ). Pore-forming polypeptides of the pathogenic protozoon Naegleria fowleri . . J Biol Chem 277:, 22353–22360. [CrossRef] [PubMed]
    [Google Scholar]
  15. Herbst R. , Marciano-Cabral F. , Leippe M. . ( 2004; ). Antimicrobial and pore-forming peptides of free-living and potentially highly pathogenic Naegleria fowleri are released from the same precursor molecule. . J Biol Chem 279:, 25955–25958. [CrossRef] [PubMed]
    [Google Scholar]
  16. Hu W. N. , Band R. N. , Kopachik W. J. . ( 1991; ). Virulence-related protein synthesis in Naegleria fowleri . . Infect Immun 59:, 4278–4282.[PubMed]
    [Google Scholar]
  17. Hu W. N. , Kopachik W. , Band R. N. . ( 1992; ). Cloning and characterization of transcripts showing virulence-related gene expression in Naegleria fowleri . . Infect Immun 60:, 2418–2424.[PubMed]
    [Google Scholar]
  18. Jamerson M. , da Rocha-Azevedo B. , Cabral G. A. , Marciano-Cabral F. . ( 2000; ). Pathogenic Naegleria fowleri and non-pathogenic Naegleria lovaniensis exhibit differential adhesion to, and invasion of, extracellular matrix proteins. . Microbiology 158:, 791–803.[PubMed] [CrossRef]
    [Google Scholar]
  19. Jarolim K. L. , McCosh J. K. , Howard M. J. , John D. T. . ( 2000; ). A light microscopy study of the migration of Naegleria fowleri from the nasal submucosa to the central nervous system during the early stage of primary amebic meningoencephalitis in mice. . J Parasitol 86:, 50–55.[PubMed] [CrossRef]
    [Google Scholar]
  20. John D. T. , Hoppe K. L. . ( 1990; ). Susceptibility of wild mammals to infection with Naegleria fowleri . . J Parasitol 76:, 865–868. [CrossRef] [PubMed]
    [Google Scholar]
  21. John D. T. , Howard M. J. . ( 1993; ). Virulence of Naegleria fowleri affected by axenic cultivation and passage in mice. . Folia Parasitol (Praha) 40:, 187–191.[PubMed]
    [Google Scholar]
  22. John D. T. , John R. A. . ( 1989; ). Cytopathogenicity of Naegleria fowleri in mammalian cell cultures. . Parasitol Res 76:, 20–25. [CrossRef] [PubMed]
    [Google Scholar]
  23. Jung S. Y. , Kim J. H. , Song K. J. , Lee Y. J. , Kwon M. H. , Kim K. , Park S. , Im K. I. , Shin H. J. . ( 2009; ). Gene silencing of nfa1 affects the in vitro cytotoxicity of Naegleria fowleri in murine macrophages. . Mol Biochem Parasitol 165:, 87–93. [CrossRef] [PubMed]
    [Google Scholar]
  24. Lee Y. J. , Kim J. H. , Jeong S. R. , Song K. J. , Kim K. , Park S. , Park M. S. , Shin H. J. . ( 2007; ). Production of Nfa1-specific monoclonal antibodies that influences the in vitro cytotoxicity of Naegleria fowleri trophozoites on microglial cells. . Parasitol Res 101:, 1191–1196. [CrossRef] [PubMed]
    [Google Scholar]
  25. Marciano-Cabral F. . ( 1988; ). Biology of Naegleria spp. . Microbiol Rev 52:, 114–133.[PubMed]
    [Google Scholar]
  26. Marciano-Cabral F. , Cabral G. A. . ( 2007; ). The immune response to Naegleria fowleri amebae and pathogenesis of infection. . FEMS Immunol Med Microbiol 51:, 243–259. [CrossRef] [PubMed]
    [Google Scholar]
  27. Martinez A. J. , Nelson E. C. , Jones M. M. , Duma R. J. , Rosenblum W. I. . ( 1971; ). Experimental Naegleria meningoencephalitis in mice. An electron microscope study. . Lab Invest 25:, 465–475.[PubMed]
    [Google Scholar]
  28. Schild M. , Gianinazzi C. , Gottstein B. , Müller N. . ( 2007; ). PCR-based diagnosis of Naegleria sp. infection in formalin-fixed and paraffin-embedded brain sections. . J Clin Microbiol 45:, 564–567. [CrossRef] [PubMed]
    [Google Scholar]
  29. Schuster F. L. . ( 2002; ). Cultivation of pathogenic and opportunistic free-living amebas. . Clin Microbiol Rev 15:, 342–354. [CrossRef] [PubMed]
    [Google Scholar]
  30. Sohn H. J. , Kim J. H. , Shin M. H. , Song K. J. , Shin H. J. . ( 2010; ). The Nf-actin gene is an important factor for food-cup formation and cytotoxicity of pathogenic Naegleria fowleri . . Parasitol Res 106:, 917–924. [CrossRef] [PubMed]
    [Google Scholar]
  31. Toney D. M. , Marciano-Cabral F. . ( 1994a; ). Modulation of complement resistance and virulence of Naegleria fowleri amoebae by alterations in growth media. . J Eukaryot Microbiol 41:, 337–343. [CrossRef] [PubMed]
    [Google Scholar]
  32. Toney D. M. , Marciano-Cabral F. . ( 1994b; ). Membrane vesiculation of Naegleria fowleri amoebae as a mechanism for resisting complement damage. . J Immunol 152:, 2952–2959.[PubMed]
    [Google Scholar]
  33. Visvesvara G. S. , Callaway C. S. . ( 1974; ). Light and electron microsopic observations on the pathogenesis of Naegleria fowleri in mouse brain and tissue culture. . J Protozool 21:, 239–250.[PubMed] [CrossRef]
    [Google Scholar]
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