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Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
EK. Herman, A. Greninger, M. van der Giezen, ML. Ginger, I. Ramirez-Macias, HC. Miller, MJ. Morgan, AD. Tsaousis, K. Velle, R. Vargová, K. Záhonová, SR. Najle, G. MacIntyre, N. Muller, M. Wittwer, DC. Zysset-Burri, M. Eliáš, CH. Slamovits, MT....
Language English Country Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
BioMedCentral
from 2003-12-01
BioMedCentral Open Access
from 2003
Directory of Open Access Journals
from 2003
Free Medical Journals
from 2003
PubMed Central
from 2003
Europe PubMed Central
from 2003
ProQuest Central
from 2009-01-01
Open Access Digital Library
from 2003-11-01
Open Access Digital Library
from 2003-01-01
Open Access Digital Library
from 2003-01-01
Medline Complete (EBSCOhost)
from 2003-11-28
Health & Medicine (ProQuest)
from 2009-01-01
ROAD: Directory of Open Access Scholarly Resources
from 2003
Springer Nature OA/Free Journals
from 2003-12-01
- MeSH
- Genomics MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Naegleria fowleri * genetics MeSH
- Transcriptome MeSH
- Trogocytosis MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. RESULTS: Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. CONCLUSIONS: In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.
Centre for Genomic Regulation 08003 Barcelona Catalonia Spain
CSIRO Indian Oceans Marine Research Centre Environomics Future Science Platform Crawley WA Australia
CSIRO Land and Water Black Mountain Laboratories Canberra Australia
Department of Biology and Ecology Faculty of Science University of Ostrava Ostrava Czech Republic
Department of Biology University of Massachusetts Amherst UK
Department of Laboratory Medicine University of Washington Medical Center Montlake USA
Department of Life Sciences The Natural History Museum London UK
Department of Medicine Faculty of Medicine and Dentistry University of Alberta Edmonton Canada
Department of Ophthalmology Inselspital Bern University Hospital University of Bern Bern Switzerland
Department of Pediatrics University of Cincinnati College of Medicine Cincinnati USA
Faculty of Science Charles University BIOCEV Prague Czech Republic
Institut de Biologia Evolutiva Barcelona Spain
Institute of Parasitology Biology Centre Czech Academy of Sciences České Budějovice Czech Republic
Institute of Parasitology Vetsuisse Faculty Bern University of Bern Bern Switzerland
School of Biosciences University of Kent Canterbury UK
Spiez Laboratory Federal Office for Civil Protection Austrasse Spiez Switzerland
References provided by Crossref.org
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