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Comparative genome sequencing reveals within-host genetic changes in Neisseria meningitidis during invasive disease

Please always quote using this URN: urn:nbn:de:bvb:20-opus-159547
  • Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanismSome members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo.show moreshow less

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Metadaten
Author: Johanna Klughammer, Marcus Dittrich, Jochen Blom, Vera Mitesser, Ulrich Vogel, Matthias Frosch, Alexander Goesmann, Tobias Müller, Christoph Schoen
URN:urn:nbn:de:bvb:20-opus-159547
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Hygiene und Mikrobiologie
Medizinische Fakultät / Institut für Humangenetik
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2017
Volume:12
Issue:1
Pagenumber:e0169892
Source:PLoS ONE 12(1): e0169892 (2017). DOI: 10.1371/journal.pone.0169892
DOI:https://doi.org/10.1371/journal.pone.0169892
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Neisseria meningitidis; blood; comparative genomics; genetic loci; genome sequencing; genomic libraries; sequence assembly tools; throat
Release Date:2018/03/28
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2017
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International