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

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 distingu...

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Autores principales: Herman, Emily K., Greninger, Alex, van der Giezen, Mark, Ginger, Michael L., Ramirez-Macias, Inmaculada, Miller, Haylea C., Morgan, Matthew J., Tsaousis, Anastasios D., Velle, Katrina, Vargová, Romana, Záhonová, Kristína, Najle, Sebastian Rodrigo, MacIntyre, Georgina, Muller, Norbert, Wittwer, Mattias, Zysset-Burri, Denise C., Eliáš, Marek, Slamovits, Claudio H., Weirauch, Matthew T., Fritz-Laylin, Lillian, Marciano-Cabral, Francine, Puzon, Geoffrey J., Walsh, Tom, Chiu, Charles, Dacks, Joel B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296547/
https://www.ncbi.nlm.nih.gov/pubmed/34294116
http://dx.doi.org/10.1186/s12915-021-01078-1
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author Herman, Emily K.
Greninger, Alex
van der Giezen, Mark
Ginger, Michael L.
Ramirez-Macias, Inmaculada
Miller, Haylea C.
Morgan, Matthew J.
Tsaousis, Anastasios D.
Velle, Katrina
Vargová, Romana
Záhonová, Kristína
Najle, Sebastian Rodrigo
MacIntyre, Georgina
Muller, Norbert
Wittwer, Mattias
Zysset-Burri, Denise C.
Eliáš, Marek
Slamovits, Claudio H.
Weirauch, Matthew T.
Fritz-Laylin, Lillian
Marciano-Cabral, Francine
Puzon, Geoffrey J.
Walsh, Tom
Chiu, Charles
Dacks, Joel B.
author_facet Herman, Emily K.
Greninger, Alex
van der Giezen, Mark
Ginger, Michael L.
Ramirez-Macias, Inmaculada
Miller, Haylea C.
Morgan, Matthew J.
Tsaousis, Anastasios D.
Velle, Katrina
Vargová, Romana
Záhonová, Kristína
Najle, Sebastian Rodrigo
MacIntyre, Georgina
Muller, Norbert
Wittwer, Mattias
Zysset-Burri, Denise C.
Eliáš, Marek
Slamovits, Claudio H.
Weirauch, Matthew T.
Fritz-Laylin, Lillian
Marciano-Cabral, Francine
Puzon, Geoffrey J.
Walsh, Tom
Chiu, Charles
Dacks, Joel B.
author_sort Herman, Emily K.
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01078-1.
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spelling pubmed-82965472021-07-22 Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri Herman, Emily K. Greninger, Alex van der Giezen, Mark Ginger, Michael L. Ramirez-Macias, Inmaculada Miller, Haylea C. Morgan, Matthew J. Tsaousis, Anastasios D. Velle, Katrina Vargová, Romana Záhonová, Kristína Najle, Sebastian Rodrigo MacIntyre, Georgina Muller, Norbert Wittwer, Mattias Zysset-Burri, Denise C. Eliáš, Marek Slamovits, Claudio H. Weirauch, Matthew T. Fritz-Laylin, Lillian Marciano-Cabral, Francine Puzon, Geoffrey J. Walsh, Tom Chiu, Charles Dacks, Joel B. BMC Biol Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01078-1. BioMed Central 2021-07-22 /pmc/articles/PMC8296547/ /pubmed/34294116 http://dx.doi.org/10.1186/s12915-021-01078-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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.
spellingShingle Research Article
Herman, Emily K.
Greninger, Alex
van der Giezen, Mark
Ginger, Michael L.
Ramirez-Macias, Inmaculada
Miller, Haylea C.
Morgan, Matthew J.
Tsaousis, Anastasios D.
Velle, Katrina
Vargová, Romana
Záhonová, Kristína
Najle, Sebastian Rodrigo
MacIntyre, Georgina
Muller, Norbert
Wittwer, Mattias
Zysset-Burri, Denise C.
Eliáš, Marek
Slamovits, Claudio H.
Weirauch, Matthew T.
Fritz-Laylin, Lillian
Marciano-Cabral, Francine
Puzon, Geoffrey J.
Walsh, Tom
Chiu, Charles
Dacks, Joel B.
Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
title Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
title_full Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
title_fullStr Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
title_full_unstemmed Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
title_short Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
title_sort genomics and transcriptomics yields a system-level view of the biology of the pathogen naegleria fowleri
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296547/
https://www.ncbi.nlm.nih.gov/pubmed/34294116
http://dx.doi.org/10.1186/s12915-021-01078-1
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