Evidence map›Paper›PMID 34294116›Full record

ArticleBMC biology2021

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 and 15 more

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 35 citations in OpenAlex.

  1. Proceedings of the National Academy of Sciences of the United States of America · 2026
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  2. International journal of environmental research and public health · 2026
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  4. bioRxiv : the preprint server for biology · 2025
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  9. Review
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  11. Review
  12. Transcriptomic profiling of "brain-eating amoeba"Frontiers in cellular and infection microbiology · 2024
    Article
  13. Lessons from the deep: mechanisms behind diversification of eukaryotic protein complexes.Biological reviews of the Cambridge Philosophical Society · 2023
    Article
  14. Article
  15. Review
  16. In Silico Structural Analysis of Serine CarboxypeptidaseInternational journal of molecular sciences · 2022
    Article
  17. Article
  18. Article
  19. Antiamoebic Properties of Metabolites againstAntibiotics (Basel, Switzerland) · 2022
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 17 institutions in 9 countries.

Emily K Herman *Division of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. eherman@ualberta.ca.
Alex Greninger *Laboratory Medicine and Medicine / Infectious Diseases, UCSF-Abbott Viral Diagnostics and Discovery Center, UCSF Clinical Microbiology Laboratory UCSF School of Medicine, San Francisco, USA.
Mark van der GiezenCentre for Organelle Research, Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.
Michael L GingerSchool of Applied Sciences, Department of Biological and Geographical Sciences, University of Huddersfield, Huddersfield, UK.
Inmaculada Ramirez-MaciasDivision of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Haylea C MillerCSIRO Land and Water, Centre for Environment and Life Sciences, Private Bag No.5, Wembley, Western Australia 6913, Australia.
Matthew J MorganCSIRO Land and Water, Black Mountain Laboratories, Canberra, Australia.
Anastasios D TsaousisSchool of Biosciences, University of Kent, Canterbury, UK.
Katrina VelleDepartment of Biology, University of Massachusetts, Amherst, UK.
Romana VargováDepartment of Biology and Ecology, Faculty of Science, University of Ostrava, Ostrava, Czech Republic.
Kristína ZáhonováDivision of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Sebastian Rodrigo NajleInstitut de Biologia Evolutiva (UPF-CSIC), Barcelona, Spain.
Georgina MacIntyreDepartment of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Norbert MullerInstitute of Parasitology, Vetsuisse Faculty Bern, University of Bern, Bern, Switzerland.
Mattias WittwerSpiez Laboratory, Federal Office for Civil Protection, Austrasse, Spiez, Switzerland.
Denise C Zysset-BurriDepartment of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Marek EliášDepartment of Biology and Ecology, Faculty of Science, University of Ostrava, Ostrava, Czech Republic.
Claudio H SlamovitsDepartment of Biochemistry and Molecular Biology, Centre for Comparative Genomics and Evolutionary Bioinformatics, Dalhousie University, Halifax, Canada.
Matthew T WeirauchCenter for Autoimmune Genomics and Etiology and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Lillian Fritz-LaylinDepartment of Biology, University of Massachusetts, Amherst, UK.
Francine Marciano-CabralDepartment of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Geoffrey J PuzonCSIRO Land and Water, Centre for Environment and Life Sciences, Private Bag No.5, Wembley, Western Australia 6913, Australia.
Tom WalshCSIRO Land and Water, Black Mountain Laboratories, Canberra, Australia.
Charles ChiuLaboratory Medicine and Medicine / Infectious Diseases, UCSF-Abbott Viral Diagnostics and Discovery Center, UCSF Clinical Microbiology Laboratory UCSF School of Medicine, San Francisco, USA.
Joel B DacksDivision of Infectious Disease, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. dacks@ualberta.ca.ORCID 0000-0003-4520-5694
University of Alberta · CACSIRO Land and Water · AUUniversity of Bern · CHUniversity of Massachusetts Amherst · USUniversity of Ostrava · CZAbbott (United States) · USAustralian Institute of Marine Science · AUCincinnati Children's Hospital Medical Center · USDalhousie University · CAInstitut de Biologia Evolutiva · ESNatural History Museum · GBOverlake Hospital Medical Center · USSpiez Laboratory · CHUniversity of Huddersfield · GBUniversity of Kent · GBUniversity of Stavanger · NOVirginia Commonwealth University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Naegleria fowleriAnimalsDisease Models, AnimalGenomicsMiceTranscriptomeTrogocytosisCytoskeletonGenome sequenceIlluminaInter-strain diversityLysosomalMetabolismNeuropathogenicProteaseRNA-Seq

Identifiers

PMID34294116
PMCPMC8296547
OpenAlexW3185964176

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.