Genome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adults
<p><strong><i>Background.</strong></i> <i>Neisseria meningitidis</i> serogroup Y, especially ST-23 clonal complex (Y:cc23), represents a larger proportion of invasive meningococcal disease (IMD) in older adults compared to younger individuals. This study exp...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2022
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| _version_ | 1797109872050831360 |
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| author | Maynard-Smith, L Derrick, JP Borrow, R Lucidarme, J Maiden, MCJ Heyderman, RS Harrison, OB |
| author_facet | Maynard-Smith, L Derrick, JP Borrow, R Lucidarme, J Maiden, MCJ Heyderman, RS Harrison, OB |
| author_sort | Maynard-Smith, L |
| collection | OXFORD |
| description | <p><strong><i>Background.</strong></i>
<i>Neisseria meningitidis</i> serogroup Y, especially ST-23 clonal complex (Y:cc23), represents a larger proportion of invasive meningococcal disease (IMD) in older adults compared to younger individuals. This study explored the meningococcal genetic variation underlying this association.</p>
<p><strong><i>Methods.</strong></i>
Maximum-likelihood phylogenies and the pangenome were analyzed using whole-genome sequence (WGS) data from 200 Y:cc23 isolates in the <i>Neisseria</i> PubMLST database. Genome-wide association studies (GWAS) were performed on WGS data from 250 Y:cc23 isolates from individuals with IMD aged ≥65 years versus < 65 years.</p>
<p><strong><i>Results.</strong></i>
Y:cc23 meningococcal variants did not cluster by age group or disease phenotype in phylogenetic analyses. Pangenome comparisons found no differences in presence or absence of genes in IMD isolates from the different age groups. GWAS identified differences in nucleotide polymorphisms within the transferrin-binding protein B (<i>tbpB</i>) gene in isolates from individuals ≥65 years of age. TbpB structure modelling suggests these may impact binding of human transferrin.</p>
<p><strong><i>Conclusions.</strong></i>
These data suggest differential iron scavenging capacity amongst Y:cc23 meningococci isolated from older compared to younger patients. Iron acquisition is essential for many bacterial pathogens including the meningococcus. These polymorphisms may facilitate colonization, thereby increasing the risk of disease in vulnerable older people with altered nasopharyngeal microbiomes and nutritional status.</p> |
| first_indexed | 2024-03-07T07:47:23Z |
| format | Journal article |
| id | oxford-uuid:b55712ee-2419-4287-b71e-b6a464bf7694 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:47:23Z |
| publishDate | 2022 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:b55712ee-2419-4287-b71e-b6a464bf76942023-06-12T15:53:29ZGenome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adultsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b55712ee-2419-4287-b71e-b6a464bf7694EnglishSymplectic ElementsOxford University Press2022Maynard-Smith, LDerrick, JPBorrow, RLucidarme, JMaiden, MCJHeyderman, RSHarrison, OB<p><strong><i>Background.</strong></i> <i>Neisseria meningitidis</i> serogroup Y, especially ST-23 clonal complex (Y:cc23), represents a larger proportion of invasive meningococcal disease (IMD) in older adults compared to younger individuals. This study explored the meningococcal genetic variation underlying this association.</p> <p><strong><i>Methods.</strong></i> Maximum-likelihood phylogenies and the pangenome were analyzed using whole-genome sequence (WGS) data from 200 Y:cc23 isolates in the <i>Neisseria</i> PubMLST database. Genome-wide association studies (GWAS) were performed on WGS data from 250 Y:cc23 isolates from individuals with IMD aged ≥65 years versus < 65 years.</p> <p><strong><i>Results.</strong></i> Y:cc23 meningococcal variants did not cluster by age group or disease phenotype in phylogenetic analyses. Pangenome comparisons found no differences in presence or absence of genes in IMD isolates from the different age groups. GWAS identified differences in nucleotide polymorphisms within the transferrin-binding protein B (<i>tbpB</i>) gene in isolates from individuals ≥65 years of age. TbpB structure modelling suggests these may impact binding of human transferrin.</p> <p><strong><i>Conclusions.</strong></i> These data suggest differential iron scavenging capacity amongst Y:cc23 meningococci isolated from older compared to younger patients. Iron acquisition is essential for many bacterial pathogens including the meningococcus. These polymorphisms may facilitate colonization, thereby increasing the risk of disease in vulnerable older people with altered nasopharyngeal microbiomes and nutritional status.</p> |
| spellingShingle | Maynard-Smith, L Derrick, JP Borrow, R Lucidarme, J Maiden, MCJ Heyderman, RS Harrison, OB Genome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adults |
| title | Genome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adults |
| title_full | Genome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adults |
| title_fullStr | Genome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adults |
| title_full_unstemmed | Genome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adults |
| title_short | Genome-wide association studies identify an association of transferrin binding protein B variation and invasive serogroup Y meningococcal disease in older adults |
| title_sort | genome wide association studies identify an association of transferrin binding protein b variation and invasive serogroup y meningococcal disease in older adults |
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