We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pneumococcal genetic variability in age-dependent bacterial carriage.
- Authors
Kremer, Philip H. C.; Ferwerda, Bart; Bootsma, Hester J.; Rots, Nienke Y.; Wijmenga-Monsuur, Alienke J.; Sanders, Elisabeth A. M.; Trzciński, Krzysztof; Wyllie, Anne L.; Turner, Paul; van der Ende, Arie; Brouwer, Matthijs C.; Bentley, Stephen D.; van de Beek, Diederik; Lees, John A.
- Abstract
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 (h² = 0.10, 95% CI 0.00-0.69) and stronger evidence in the second cohort (h² = 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 (h²serotype = 0.07, 95% CI 0.04-0.14 and h²GPSC = 0.06, 95% CI 0.03-0.13) and the second cohort (h²serotype = 0.11, 95% CI 0.05-0.21 and h²GPSC = 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.
- Subjects
GENETIC variation; GENOME-wide association studies; SINGLE nucleotide polymorphisms; HERITABILITY; NUCLEOTIDE sequencing; GENE clusters
- Publication
eLife, 2022, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.69244