Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
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Author(s)
Type
Journal Article
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.
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.
Date Issued
2017-07-25
Date Acceptance
2017-07-21
Citation
eLife, 2017, 6
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Journal / Book Title
eLife
Volume
6
Copyright Statement
Copyright Lees et al. This
article is distributed under the
terms of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited.
article is distributed under the
terms of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited.
License URL
Sponsor
Medical Research Council (MRC)
Grant Number
MR/K010174/1B
Subjects
Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
STREPTOCOCCUS-PNEUMONIAE
TRANSMISSION PARAMETERS
EPIDEMIOLOGIC EVIDENCE
BACTERIAL PHENOTYPES
ACQUIRED-IMMUNITY
INVASIVE-DISEASE
COMPLEX TRAITS
GENETIC-BASIS
EVOLUTION
SEROTYPE
Publication Status
Published
Article Number
e26255