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Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis

Meningococcal disease is a widely distributed complex disease affecting all age categories. It can cause severe meningitis and septicemia, especially in unvaccinated infants and young children. The causative agent, Neisseria meningitidis (Nm), can be phenotypically and genetically differentiated int...

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Autores principales: Hao, Weilong, Ma, Jennifer H., Warren, Keisha, Tsang, Raymond S.W., Low, Donald E., Jamieson, Frances B., Alexander, David C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242501/
https://www.ncbi.nlm.nih.gov/pubmed/22084315
http://dx.doi.org/10.1093/gbe/evr119
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author Hao, Weilong
Ma, Jennifer H.
Warren, Keisha
Tsang, Raymond S.W.
Low, Donald E.
Jamieson, Frances B.
Alexander, David C.
author_facet Hao, Weilong
Ma, Jennifer H.
Warren, Keisha
Tsang, Raymond S.W.
Low, Donald E.
Jamieson, Frances B.
Alexander, David C.
author_sort Hao, Weilong
collection PubMed
description Meningococcal disease is a widely distributed complex disease affecting all age categories. It can cause severe meningitis and septicemia, especially in unvaccinated infants and young children. The causative agent, Neisseria meningitidis (Nm), can be phenotypically and genetically differentiated into serogroups and sequence types (STs) and has a highly dynamic population structure. To obtain a deeper understanding of the epidemiology of Nm, we sequenced seven Nm genomes. Large-scale genomic analysis was conducted with these 7 Nm genomes, 27 additional Nm genomes from GenBank, and 4 other Neisseria genomes. We observed extensive homologous recombination in all gene functional categories among different Nm genomes. Homologous recombination is so frequent that it has resulted in numerous chimeric open reading frames, including genes in the capsule biosynthesis cluster and loci targeted by commercial vaccines. Our results reveal that, despite widespread use, evolutionary relationships inferred from the standard seven-gene multilocus sequence typing (MLST) method could not predict virulence gene content or strain phenotype. In fact, up to 28% of the virulence-associated genes could differ between strains of identical STs. Consistent with previous studies, we found that allelic recombination is also associated with alterations in antibiotic susceptibility. Overall, these findings emphasize the extensive genomic plasticity of Nm and the limitations of standard molecular methods to quantify this genotypic and phenotypic diversity.
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spelling pubmed-32425012011-12-19 Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis Hao, Weilong Ma, Jennifer H. Warren, Keisha Tsang, Raymond S.W. Low, Donald E. Jamieson, Frances B. Alexander, David C. Genome Biol Evol Research Articles Meningococcal disease is a widely distributed complex disease affecting all age categories. It can cause severe meningitis and septicemia, especially in unvaccinated infants and young children. The causative agent, Neisseria meningitidis (Nm), can be phenotypically and genetically differentiated into serogroups and sequence types (STs) and has a highly dynamic population structure. To obtain a deeper understanding of the epidemiology of Nm, we sequenced seven Nm genomes. Large-scale genomic analysis was conducted with these 7 Nm genomes, 27 additional Nm genomes from GenBank, and 4 other Neisseria genomes. We observed extensive homologous recombination in all gene functional categories among different Nm genomes. Homologous recombination is so frequent that it has resulted in numerous chimeric open reading frames, including genes in the capsule biosynthesis cluster and loci targeted by commercial vaccines. Our results reveal that, despite widespread use, evolutionary relationships inferred from the standard seven-gene multilocus sequence typing (MLST) method could not predict virulence gene content or strain phenotype. In fact, up to 28% of the virulence-associated genes could differ between strains of identical STs. Consistent with previous studies, we found that allelic recombination is also associated with alterations in antibiotic susceptibility. Overall, these findings emphasize the extensive genomic plasticity of Nm and the limitations of standard molecular methods to quantify this genotypic and phenotypic diversity. Oxford University Press 2011-11-14 /pmc/articles/PMC3242501/ /pubmed/22084315 http://dx.doi.org/10.1093/gbe/evr119 Text en © The Author(s) 2011. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Hao, Weilong
Ma, Jennifer H.
Warren, Keisha
Tsang, Raymond S.W.
Low, Donald E.
Jamieson, Frances B.
Alexander, David C.
Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis
title Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis
title_full Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis
title_fullStr Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis
title_full_unstemmed Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis
title_short Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis
title_sort extensive genomic variation within clonal complexes of neisseria meningitidis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242501/
https://www.ncbi.nlm.nih.gov/pubmed/22084315
http://dx.doi.org/10.1093/gbe/evr119
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