Dataset Information

Genome-Wide Association Studies Identify an Association of Transferrin Binding Protein B Variation and Invasive Serogroup Y Meningococcal Disease in Older Adults.

ABSTRACT:

Background

Neisseria meningitidis 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.

Methods

Maximum-likelihood phylogenies and the pangenome were analyzed using whole-genome sequence (WGS) data from 200 Y:cc23 isolates in the Neisseria 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.

Results

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 (tbpB) gene in isolates from individuals ≥65 years of age. TbpB structure modelling suggests these may impact binding of human transferrin.

Conclusions

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.

SUBMITTER: Maynard-Smith L

PROVIDER: S-EPMC9748998 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Genome-Wide Association Studies Identify an Association of Transferrin Binding Protein B Variation and Invasive Serogroup Y Meningococcal Disease in Older Adults.

Maynard-Smith Laura L Derrick Jeremy P JP Borrow Ray R Lucidarme Jay J Maiden Martin C J MCJ Heyderman Robert S RS Harrison Odile B OB

The Journal of infectious diseases 20221201 12

<h4>Background</h4>Neisseria meningitidis 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.<h4>Methods</h4>Maximum-likelihood phylogenies and the pangenome were analyzed using whole-genome sequence (WGS) data from 200 Y:cc23 isolates in the Neisseria PubMLST database. Genome-wide associati ...[more]

PMID: 36322504

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Project description:The bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.

Project description:Despite its effectiveness in preventing invasive meningococcal disease (IMD), pediatric uptake of recombinant meningococcal vaccination for serogroup B meningitis (MenB) is low in Italy. This study aimed to investigate knowledge, attitudes, and practice (KAP) about IMD and the vaccine uptake for MenB from July to December 2019, in a sample collected from a series of local Facebook discussion groups from the provinces of Parma and Reggio Emilia (North-Eastern Italy; 337,104 registered users). A self-administered anonymous web-based questionnaire was used to collect demographics, knowledge status, perceived risk for contracting meningitis, attitude towards the utility of meningococcal vaccine, and willingness to receive/perform MenB vaccine in their offspring. In total, 541 parents returned a fully completed questionnaire (response rate of 1.6% of potential recipients), with a mean age of 39.2 years ± 6.3 (78.1% females). Meningococcal infection was identified as severe or highly severe by most participants (88.9%), while it was recognized as being frequent/highly frequent in the general population by 18.6% of respondents. The overall knowledge status was unsatisfactory (57.6% ± 33.6 of correct answers to the knowledge test). Even though 63.4% of participants were somewhat favorable to MenB/MenC vaccines, offspring's vaccination towards MenB was reported by only 38.7% of participants. In a binary logistic regression model, the male gender of respondents (adjusted odds ratio [aOR] 3.184, 95% confidence interval [95%CI] 1.772 to 5.721), living in a municipality >15,000 inhabitants (aOR 1.675, 95%CI 1.051 to 2.668), reporting a favorable attitude on meningococcus B vaccine (aOR 12.472, 95%CI 3.030 to 51.338), having been vaccinated against serogroup B (aOR 5.624, 95%CI 1.936 to 16.337) and/or serogroup C (aOR 2.652, 95%CI 1.442 to 4.872), and having previously vaccinated their offspring against serogroup C meningococcus (aOR 6.585, 95%CI 3.648 to 11.888) were characterized as positive effectors of offspring's vaccination. On the contrary, having a higher risk perception on vaccines was identified as the only negative effector (aOR 0.429, 95%CI 0.241 to 0.765). Our results hint towards extensive knowledge gaps on IMD and preventive interventions in the general population, suggesting that a positive attitude towards vaccines and vaccinations could be identified as the main effector also for MenB acceptance. Interventions in the general population aimed at improving confidence, compliance, and acknowledgment of the collective responsibility, as well as preventing actual constraints and the sharing of false beliefs on infectious diseases and their preventive measures, could therefore increase vaccination acceptance in both targeted individuals and their offspring.

Dataset Information

Genome-Wide Association Studies Identify an Association of Transferrin Binding Protein B Variation and Invasive Serogroup Y Meningococcal Disease in Older Adults.

Background

Methods

Results

Conclusions

Publications

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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