Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri
1 Biology Division, Spiez Laboratory, Federal Office for Civil Protection, Austrasse, CH-3700 Spiez, Switzerland
2 Institute of Parasitology, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland
3 Graduate School for Cellular and Biomedical Sciences, University of Bern, Freiestrasse 1, CH-3012 Bern, Switzerland
4 Mass Spectrometry and Proteomics, Department of Clinical Research, University Hospital, Bern CH-3010, Switzerland
BMC Genomics 2014, 15:496 doi:10.1186/1471-2164-15-496Published: 19 June 2014
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.
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.
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.