title: Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Zysset-Burri
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Beuret
authors.forename: Manfred
authors.initials: M
authors.lastname: Heller
authors.forename: Nadia
authors.initials: N
authors.lastname: Schürch
authors.forename: Bruno
authors.initials: B
authors.lastname: Gottstein
authors.affiliation: Biology Division, Spiez Laboratory, Federal Office for Civil Protection, Austrasse, CH-3700 Spiez, Switzerland. matthias.wittwer@babs.admin.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wittwer
mesh_terms: D000562:Amebiasis / Q000469:parasitology; D020808:Central Nervous System Protozoal Infections / Q000469:parasitology; D016678:Genome; D006801:Humans; D058977:Molecular Sequence Annotation; D016848:Naegleria fowleri / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D059467:Transcriptome; D037521:Virulence Factors / Q000235:genetics
chemical_list: D020543:Proteome; D015800:Protozoan Proteins; D037521:Virulence Factors