Development of a high- versus low-pathogenicity model of the free-living amoeba Naegleria fowleri

Zysset-Burri, Denise Corinne; Gottstein, Bruno; Zumkehr, Béatrice; Hemphill, Andrew; Schürch, Nadia; Wittwer, Matthias; Müller, Norbert (2012). Development of a high- versus low-pathogenicity model of the free-living amoeba Naegleria fowleri. Microbiology, 158(Pt 10), pp. 2652-2660. Society for General Microbiology 10.1099/mic.0.059790-0

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Species in the genus Naegleria are free-living amoebae of the soil and warm fresh water. Although around 30 species have been recognized, Naegleria fowleri 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 N. fowleri 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 N. fowleri 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 in vitro cytotoxicity and in vivo pathogenicity of N. fowleri. Trophozoites maintained in Nelson's medium were highly pathogenic for mice, demonstrated rapid in vitro 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, N. fowleri 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 in vitro, diminished cell diameter and contact-dependent target cell destruction. Thus, in this model, the presence of LH resulted in increased proliferation of trophozoites in vitro and enhanced pathogenicity of N. fowleri in mice. However, neither in vitro 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 N. fowleri remains a complex interaction between as-yet-unidentified cellular mechanisms.

Item Type:	Journal Article (Original Article)
Division/Institute:	05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology 05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction 04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases 05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
UniBE Contributor:	Zysset, Denise Corinne, Gottstein, Bruno, Zumkehr, Béatrice, Hemphill, Andrew, Wittwer, Matthias, Müller, Norbert
Subjects:	600 Technology > 630 Agriculture 500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	1350-0872
Publisher:	Society for General Microbiology
Language:	English
Submitter:	Matthias Wittwer
Date Deposited:	20 Jun 2014 13:15
Last Modified:	05 Dec 2022 14:34
Publisher DOI:	10.1099/mic.0.059790-0
PubMed ID:	22878396
URI:	https://boris.unibe.ch/id/eprint/52868