Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri

BMC Biology

Matthew J. Morgan¹  Tom Walsh¹  Geoffrey J. Puzon²  Haylea C. Miller³  Matthew T. Weirauch⁴  Mark van der Giezen⁵  Claudio H. Slamovits⁶  Marek Eliáš⁷  Romana Vargová⁷  Katrina Velle⁸  Lillian Fritz-Laylin⁸  Georgina MacIntyre⁹  Francine Marciano-Cabral^1,10  Denise C. Zysset-Burri^1,11  Emily K. Herman^1,12  Inmaculada Ramirez-Macias^1,13  Kristína Záhonová^1,14  Joel B. Dacks^1,15  Sebastian Rodrigo Najle^1,16  Norbert Muller^1,17  Charles Chiu^1,18  Alex Greninger^1,19  Michael L. Ginger^2,20  Anastasios D. Tsaousis^2,21  Mattias Wittwer^2,22 

[1] CSIRO Land and Water, Black Mountain Laboratories, Canberra, Australia;CSIRO Land and Water, Centre for Environment and Life Sciences, Private Bag No.5, Wembley, Western Australia 6913, Australia;CSIRO Land and Water, Centre for Environment and Life Sciences, Private Bag No.5, Wembley, Western Australia 6913, Australia;CSIRO, Indian Oceans Marine Research Centre, Environomics Future Science Platform, Crawley, WA, Australia;Center for Autoimmune Genomics and Etiology and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, USA;Centre for Organelle Research, Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway;Department of Biochemistry and Molecular Biology, Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Canada;Department of Biology and Ecology, Faculty of Science, University of Ostrava, Ostrava, Czech Republic;Department of Biology, University of Massachusetts, Amherst, UK;Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada;Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA;Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland;Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada;Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada;Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada;Department of Cardiology, Hospital Clinico Universitario Virgen de la Arrixaca. Instituto Murciano de Investigación Biosanitaria. Centro de Investigación Biomedica en Red-Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain;Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada;Faculty of Science, Charles University, BIOCEV, Prague, Czech Republic;Institute of Parasitology, Biology Centre, Czech Academy of Sciences, České Budějovice, Czech Republic;Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada;Institute of Parasitology, Biology Centre, Czech Academy of Sciences, České Budějovice, Czech Republic;Department of Life Sciences, The Natural History Museum, London, UK;Institut de Biologia Evolutiva (UPF-CSIC), Barcelona, Spain;Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08003, Barcelona, Catalonia, Spain;Institute of Parasitology, Vetsuisse Faculty Bern, University of Bern, Bern, Switzerland;Laboratory Medicine and Medicine / Infectious Diseases, UCSF-Abbott Viral Diagnostics and Discovery Center, UCSF Clinical Microbiology Laboratory UCSF School of Medicine, San Francisco, USA;Laboratory Medicine and Medicine / Infectious Diseases, UCSF-Abbott Viral Diagnostics and Discovery Center, UCSF Clinical Microbiology Laboratory UCSF School of Medicine, San Francisco, USA;Department of Laboratory Medicine, University of Washington Medical Center, Montlake, USA;School of Applied Sciences, Department of Biological and Geographical Sciences, University of Huddersfield, Huddersfield, UK;School of Biosciences, University of Kent, Canterbury, UK;Spiez Laboratory, Federal Office for Civil Protection, Austrasse, Spiez, Switzerland;

关键词: Illumina;    RNA-Seq;    Genome sequence;    Protease;    Cytoskeleton;    Metabolism;    Lysosomal;    Inter-strain diversity;    Neuropathogenic;   

DOI  :  10.1186/s12915-021-01078-1

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsHere, 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.ConclusionsIn-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.

【 授权许可】

CC BY