Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
Emily K. Herman,
Alex Greninger,
Mark van der Giezen,
Michael L. Ginger,
Inmaculada Ramirez-Macias,
Haylea C. Miller,
Matthew J. Morgan,
Anastasios D. Tsaousis,
Katrina Velle,
Romana Vargová,
Kristína Záhonová,
Sebastian Rodrigo Najle,
Georgina MacIntyre,
Norbert Muller,
Mattias Wittwer,
Denise C. Zysset-Burri,
Marek Eliáš,
Claudio H. Slamovits,
Matthew T. Weirauch,
Lillian Fritz-Laylin,
Francine Marciano-Cabral,
Geoffrey J. Puzon,
Tom Walsh,
Charles Chiu,
Joel B. Dacks
Affiliations
Emily K. Herman
Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta
Alex Greninger
Laboratory Medicine and Medicine / Infectious Diseases, UCSF-Abbott Viral Diagnostics and Discovery Center, UCSF Clinical Microbiology Laboratory UCSF School of Medicine
Mark van der Giezen
Centre for Organelle Research, Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger
Michael L. Ginger
School of Applied Sciences, Department of Biological and Geographical Sciences, University of Huddersfield
Inmaculada Ramirez-Macias
Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta
Haylea C. Miller
CSIRO Land and Water, Centre for Environment and Life Sciences
Matthew J. Morgan
CSIRO Land and Water, Black Mountain Laboratories
Anastasios D. Tsaousis
School of Biosciences, University of Kent
Katrina Velle
Department of Biology, University of Massachusetts
Romana Vargová
Department of Biology and Ecology, Faculty of Science, University of Ostrava
Kristína Záhonová
Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta
Sebastian Rodrigo Najle
Institut de Biologia Evolutiva (UPF-CSIC)
Georgina MacIntyre
Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta
Norbert Muller
Institute of Parasitology, Vetsuisse Faculty Bern, University of Bern
Mattias Wittwer
Spiez Laboratory, Federal Office for Civil Protection
Denise C. Zysset-Burri
Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern
Marek Eliáš
Department of Biology and Ecology, Faculty of Science, University of Ostrava
Claudio H. Slamovits
Department of Biochemistry and Molecular Biology, Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University
Matthew T. Weirauch
Center for Autoimmune Genomics and Etiology and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children’s Hospital Medical Center
Lillian Fritz-Laylin
Department of Biology, University of Massachusetts
Francine Marciano-Cabral
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine
Geoffrey J. Puzon
CSIRO Land and Water, Centre for Environment and Life Sciences
Tom Walsh
CSIRO Land and Water, Black Mountain Laboratories
Charles Chiu
Laboratory Medicine and Medicine / Infectious Diseases, UCSF-Abbott Viral Diagnostics and Discovery Center, UCSF Clinical Microbiology Laboratory UCSF School of Medicine
Joel B. Dacks
Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta
Abstract 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.
