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Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis
Neisseria meningitidis , the meningococcus, resides exclusively in humans and causes invasive meningococcal disease (IMD). The population of N. meningitidis is structured into stable clonal complexes by limited horizontal recombination in this naturally transformable species. N. meningitidis is an o...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Microbiology Society
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627216/ https://www.ncbi.nlm.nih.gov/pubmed/34704920 http://dx.doi.org/10.1099/mgen.0.000662 |
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author | Mullally, Christopher A. Mikucki, August Wise, Michael J. Kahler, Charlene M. |
author_facet | Mullally, Christopher A. Mikucki, August Wise, Michael J. Kahler, Charlene M. |
author_sort | Mullally, Christopher A. |
collection | PubMed |
description | Neisseria meningitidis , the meningococcus, resides exclusively in humans and causes invasive meningococcal disease (IMD). The population of N. meningitidis is structured into stable clonal complexes by limited horizontal recombination in this naturally transformable species. N. meningitidis is an opportunistic pathogen, with some clonal complexes, such as cc53, effectively acting as commensal colonizers, while other genetic lineages, such as cc11, are rarely colonizers but are over-represented in IMD and are termed hypervirulent. This study examined theoretical evolutionary pathways for pathogenic and commensal lineages by examining the prevalence of horizontally acquired genomic islands (GIs) and loss-of-function (LOF) mutations. Using a collection of 4850 genomes from the BIGSdb database, we identified 82 GIs in the pan-genome of 11 lineages (10 hypervirulent and one commensal lineage). A new computational tool, Phaser, was used to identify frameshift mutations, which were examined for statistically significant association with genetic lineage. Phaser identified a total of 144 frameshift loci of which 105 were shown to have a statistically significant non-random distribution in phase status. The 82 GIs, but not the LOF loci, were associated with genetic lineage and invasiveness using the disease carriage ratio metric. These observations have been integrated into a new model that infers the early events of the evolution of the human adapted meningococcus. These pathways are enriched for GIs that are involved in modulating attachment to the host, growth rate, iron uptake and toxin expression which are proposed to increase competition within the meningococcal population for the limited environmental niche of the human nasopharynx. We surmise that competition for the host mucosal surface with the nasopharyngeal microbiome has led to the selection of isolates with traits that enable access to cell types (non-phagocytic and phagocytic) in the submucosal tissues leading to an increased risk for IMD. |
format | Online Article Text |
id | pubmed-8627216 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Microbiology Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-86272162021-11-29 Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis Mullally, Christopher A. Mikucki, August Wise, Michael J. Kahler, Charlene M. Microb Genom Research Articles Neisseria meningitidis , the meningococcus, resides exclusively in humans and causes invasive meningococcal disease (IMD). The population of N. meningitidis is structured into stable clonal complexes by limited horizontal recombination in this naturally transformable species. N. meningitidis is an opportunistic pathogen, with some clonal complexes, such as cc53, effectively acting as commensal colonizers, while other genetic lineages, such as cc11, are rarely colonizers but are over-represented in IMD and are termed hypervirulent. This study examined theoretical evolutionary pathways for pathogenic and commensal lineages by examining the prevalence of horizontally acquired genomic islands (GIs) and loss-of-function (LOF) mutations. Using a collection of 4850 genomes from the BIGSdb database, we identified 82 GIs in the pan-genome of 11 lineages (10 hypervirulent and one commensal lineage). A new computational tool, Phaser, was used to identify frameshift mutations, which were examined for statistically significant association with genetic lineage. Phaser identified a total of 144 frameshift loci of which 105 were shown to have a statistically significant non-random distribution in phase status. The 82 GIs, but not the LOF loci, were associated with genetic lineage and invasiveness using the disease carriage ratio metric. These observations have been integrated into a new model that infers the early events of the evolution of the human adapted meningococcus. These pathways are enriched for GIs that are involved in modulating attachment to the host, growth rate, iron uptake and toxin expression which are proposed to increase competition within the meningococcal population for the limited environmental niche of the human nasopharynx. We surmise that competition for the host mucosal surface with the nasopharyngeal microbiome has led to the selection of isolates with traits that enable access to cell types (non-phagocytic and phagocytic) in the submucosal tissues leading to an increased risk for IMD. Microbiology Society 2021-10-27 /pmc/articles/PMC8627216/ /pubmed/34704920 http://dx.doi.org/10.1099/mgen.0.000662 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution. |
spellingShingle | Research Articles Mullally, Christopher A. Mikucki, August Wise, Michael J. Kahler, Charlene M. Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis |
title | Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis
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title_full | Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis
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title_fullStr | Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis
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title_full_unstemmed | Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis
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title_short | Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis
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title_sort | modelling evolutionary pathways for commensalism and hypervirulence in neisseria meningitidis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627216/ https://www.ncbi.nlm.nih.gov/pubmed/34704920 http://dx.doi.org/10.1099/mgen.0.000662 |
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