Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
- Wellcome Trust Sanger Institute, United Kingdom
- Imperial College London, United Kingdom
- University College London, United Kingdom
- Mahidol University, Thailand
- Wellcome Trust Sanger Centre, United Kingdom
- Angkor Hospital for Children, Cambodia
Abstract
Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance.
Data availability
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Dense genomic sampling identifies highways of pneumococcal recombinationPublicly available in the NCBI Sequencing Read Archive (SRA) under study accessions ERP000435, ERP000483, ERP000485, ERP000487, ERP000598 and ERP000599.
Article and author information
Author details
Nicholas J Croucher
Funding
Wellcome (98051)
- John A Lees
- Julian Parkhill
- Stephen D Bentley
Medical Research Council (1365620)
- John A Lees
Royal Society (104169/Z/14/Z)
- Nicholas J Croucher
Royal Society (104169/Z/14/Z)
- Nicholas J Croucher
Wellcome (083735/Z/07/Z)
- Paul Turner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sarah Cobey, University of Chicago, United States
Ethics
Human subjects: Written informed consent was obtained from the mothers prior to study enrolment. Ethical approval was granted by the ethics committees of the Faculty of Tropical Medicine, Mahidol University, Thailand (MUTM-2009-306) and Oxford University, UK (OXTREC-031-06).
Version history
- Received: February 22, 2017
- Accepted: July 21, 2017
- Accepted Manuscript published: July 25, 2017 (version 1)
- Version of Record published: August 29, 2017 (version 2)
Copyright
© 2017, Lees et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
eLife 6:e26255.
https://doi.org/10.7554/eLife.26255
Further reading
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- Medicine
- Microbiology and Infectious Disease
- Epidemiology and Global Health
- Immunology and Inflammation
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