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Pneumococcal genetic variability in age-dependent bacterial carriage

The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could...

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Autores principales: Kremer, Philip HC, Ferwerda, Bart, Bootsma, Hester J, Rots, Nienke Y, Wijmenga-Monsuur, Alienke J, Sanders, Elisabeth AM, Trzciński, Krzysztof, Wyllie, Anne L, Turner, Paul, van der Ende, Arie, Brouwer, Matthijs C, Bentley, Stephen D, van de Beek, Diederik, Lees, John A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395192/
https://www.ncbi.nlm.nih.gov/pubmed/35881438
http://dx.doi.org/10.7554/eLife.69244
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author Kremer, Philip HC
Ferwerda, Bart
Bootsma, Hester J
Rots, Nienke Y
Wijmenga-Monsuur, Alienke J
Sanders, Elisabeth AM
Trzciński, Krzysztof
Wyllie, Anne L
Turner, Paul
van der Ende, Arie
Brouwer, Matthijs C
Bentley, Stephen D
van de Beek, Diederik
Lees, John A
author_facet Kremer, Philip HC
Ferwerda, Bart
Bootsma, Hester J
Rots, Nienke Y
Wijmenga-Monsuur, Alienke J
Sanders, Elisabeth AM
Trzciński, Krzysztof
Wyllie, Anne L
Turner, Paul
van der Ende, Arie
Brouwer, Matthijs C
Bentley, Stephen D
van de Beek, Diederik
Lees, John A
author_sort Kremer, Philip HC
collection PubMed
description The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefore performed genome sequencing in a large carriage cohort of children and adults and combined this with data from an existing age-stratified carriage study. We compiled a dictionary of pathogen genetic variation, including serotype, strain, sequence elements, single-nucleotide polymorphisms (SNPs), and clusters of orthologous genes (COGs) for each cohort – all of which were used in a genome-wide association with host age. Age-dependent colonization showed weak evidence of being heritable in the first cohort (h(2) = 0.10, 95% CI 0.00–0.69) and stronger evidence in the second cohort (h(2) = 0.56, 95% CI 0.23–0.87). We found that serotypes and genetic background (strain) explained a proportion of the heritability in the first cohort (h(2)(serotype) = 0.07, 95% CI 0.04–0.14 and h(2)(GPSC) = 0.06, 95% CI 0.03–0.13) and the second cohort (h(2)(serotype) = 0.11, 95% CI 0.05–0.21 and h(2)(GPSC) = 0.20, 95% CI 0.12–0.31). In a meta-analysis of these cohorts, we found one candidate association (p=1.2 × 10(-9)) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, while we did find a small effect of pathogen genome variation on pneumococcal carriage between child and adult hosts, this was variable between populations and does not appear to be caused by strong effects of individual genes. This supports proposals for adaptive future vaccination strategies that are primarily targeted at dominant circulating serotypes and tailored to the composition of the pathogen populations.
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spelling pubmed-93951922022-08-23 Pneumococcal genetic variability in age-dependent bacterial carriage Kremer, Philip HC Ferwerda, Bart Bootsma, Hester J Rots, Nienke Y Wijmenga-Monsuur, Alienke J Sanders, Elisabeth AM Trzciński, Krzysztof Wyllie, Anne L Turner, Paul van der Ende, Arie Brouwer, Matthijs C Bentley, Stephen D van de Beek, Diederik Lees, John A eLife Genetics and Genomics The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefore performed genome sequencing in a large carriage cohort of children and adults and combined this with data from an existing age-stratified carriage study. We compiled a dictionary of pathogen genetic variation, including serotype, strain, sequence elements, single-nucleotide polymorphisms (SNPs), and clusters of orthologous genes (COGs) for each cohort – all of which were used in a genome-wide association with host age. Age-dependent colonization showed weak evidence of being heritable in the first cohort (h(2) = 0.10, 95% CI 0.00–0.69) and stronger evidence in the second cohort (h(2) = 0.56, 95% CI 0.23–0.87). We found that serotypes and genetic background (strain) explained a proportion of the heritability in the first cohort (h(2)(serotype) = 0.07, 95% CI 0.04–0.14 and h(2)(GPSC) = 0.06, 95% CI 0.03–0.13) and the second cohort (h(2)(serotype) = 0.11, 95% CI 0.05–0.21 and h(2)(GPSC) = 0.20, 95% CI 0.12–0.31). In a meta-analysis of these cohorts, we found one candidate association (p=1.2 × 10(-9)) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, while we did find a small effect of pathogen genome variation on pneumococcal carriage between child and adult hosts, this was variable between populations and does not appear to be caused by strong effects of individual genes. This supports proposals for adaptive future vaccination strategies that are primarily targeted at dominant circulating serotypes and tailored to the composition of the pathogen populations. eLife Sciences Publications, Ltd 2022-07-26 /pmc/articles/PMC9395192/ /pubmed/35881438 http://dx.doi.org/10.7554/eLife.69244 Text en © 2022, Kremer et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genetics and Genomics
Kremer, Philip HC
Ferwerda, Bart
Bootsma, Hester J
Rots, Nienke Y
Wijmenga-Monsuur, Alienke J
Sanders, Elisabeth AM
Trzciński, Krzysztof
Wyllie, Anne L
Turner, Paul
van der Ende, Arie
Brouwer, Matthijs C
Bentley, Stephen D
van de Beek, Diederik
Lees, John A
Pneumococcal genetic variability in age-dependent bacterial carriage
title Pneumococcal genetic variability in age-dependent bacterial carriage
title_full Pneumococcal genetic variability in age-dependent bacterial carriage
title_fullStr Pneumococcal genetic variability in age-dependent bacterial carriage
title_full_unstemmed Pneumococcal genetic variability in age-dependent bacterial carriage
title_short Pneumococcal genetic variability in age-dependent bacterial carriage
title_sort pneumococcal genetic variability in age-dependent bacterial carriage
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395192/
https://www.ncbi.nlm.nih.gov/pubmed/35881438
http://dx.doi.org/10.7554/eLife.69244
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