1. Genetics and Genomics
  2. Microbiology and Infectious Disease
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Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration

  1. John A Lees  Is a corresponding author
  2. Nicholas J Croucher
  3. David Goldblatt
  4. François Nosten
  5. Julian Parkhill
  6. Claudia Turner
  7. Paul Turner
  8. Stephen D Bentley  Is a corresponding author
  1. Wellcome Trust Sanger Institute, United Kingdom
  2. Imperial College London, United Kingdom
  3. University College London, United Kingdom
  4. Mahidol University, Thailand
  5. Wellcome Trust Sanger Centre, United Kingdom
  6. Angkor Hospital for Children, Cambodia
Research Article
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Cite this article as: eLife 2017;6:e26255 doi: 10.7554/eLife.26255

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.

Article and author information

Author details

  1. John A Lees

    Infection Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    For correspondence
    jl11@sanger.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5360-1254
  2. Nicholas J Croucher

    Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6303-8768
  3. David Goldblatt

    Institute of Child Health, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. François Nosten

    Shoklo Malaria Research Unit, Mahidol University, Mae Sot, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7951-0745
  5. Julian Parkhill

    Infection Genomics, Wellcome Trust Sanger Centre, Hinxton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Claudia Turner

    Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
    Competing interests
    The authors declare that no competing interests exist.
  7. Paul Turner

    Shoklo Malaria Research Unit, Mahidol University, Mae Sot, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1013-7815
  8. Stephen D Bentley

    Infection Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    For correspondence
    sdb@sanger.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

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.

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).

Reviewing Editor

  1. Sarah Cobey, University of Chicago, United States

Publication history

  1. Received: February 22, 2017
  2. Accepted: July 21, 2017
  3. Accepted Manuscript published: July 25, 2017 (version 1)
  4. 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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