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

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dc.contributor.author Herman, Emily K.
dc.contributor.author Najle, Sebastián R.
dc.contributor.author Dacks, Joel B.
dc.date.accessioned 2021-11-30T07:16:50Z
dc.date.available 2021-11-30T07:16:50Z
dc.date.issued 2021
dc.identifier.citation Herman EK, Greninger A, van der Giezen M, Ginger ML, Ramirez-Macias I, Miller HC et al. Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri. BMC Biol. 2021;19(1):142. DOI: 10.1186/s12915-021-01078-1
dc.identifier.issn 1741-7007
dc.identifier.uri http://hdl.handle.net/10230/49089
dc.description.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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof BMC Biol. 2021;19(1):142
dc.rights © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s12915-021-01078-1
dc.subject.keyword Cytoskeleton
dc.subject.keyword Genome sequence
dc.subject.keyword Illumina
dc.subject.keyword Inter-strain diversity
dc.subject.keyword Lysosomal
dc.subject.keyword Metabolism
dc.subject.keyword Neuropathogenic
dc.subject.keyword Protease
dc.subject.keyword RNA-Seq
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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