Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri.

Zysset-Burri, Denise Corinne; Müller, Norbert; Beuret, Christian; Heller, Manfred; Schürch, Nadia; Gottstein, Bruno; Wittwer, Matthias (2014). Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri. BMC Genomics, 15, p. 496. BioMed Central 10.1186/1471-2164-15-496

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BACKGROUND The free-living amoeba Naegleria fowleri is the causative agent of the rapidly progressing and typically fatal primary amoebic meningoencephalitis (PAM) in humans. Despite the devastating nature of this disease, which results in > 97% mortality, knowledge of the pathogenic mechanisms of the amoeba is incomplete. This work presents a comparative proteomic approach based on an experimental model in which the pathogenic potential of N. fowleri trophozoites is influenced by the compositions of different media. RESULTS As a scaffold for proteomic analysis, we sequenced the genome and transcriptome of N. fowleri. Since the sequence similarity of the recently published genome of Naegleria gruberi was far lower than the close taxonomic relationship of these species would suggest, a de novo sequencing approach was chosen. After excluding cell regulatory mechanisms originating from different media compositions, we identified 22 proteins with a potential role in the pathogenesis of PAM. Functional annotation of these proteins revealed, that the membrane is the major location where the amoeba exerts its pathogenic potential, possibly involving actin-dependent processes such as intracellular trafficking via vesicles. CONCLUSION This study describes for the first time the 30 Mb-genome and the transcriptome sequence of N. fowleri and provides the basis for the further definition of effective intervention strategies against the rare but highly fatal form of amoebic meningoencephalitis.

Item Type:

Journal Article (Original Article)

Division/Institute:

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) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Massenspektrometrie- und Proteomics-Labor

UniBE Contributor:

Zysset-Burri, Denise Corinne; Müller, Norbert; Heller, Manfred; Gottstein, Bruno and Wittwer, Matthias

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1471-2164

Publisher:

BioMed Central

Language:

English

Submitter:

Bruno Gottstein

Date Deposited:

17 Feb 2015 14:01

Last Modified:

13 Oct 2015 15:26

Publisher DOI:

10.1186/1471-2164-15-496

PubMed ID:

24950717

BORIS DOI:

10.7892/boris.63068

URI:

https://boris.unibe.ch/id/eprint/63068

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