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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.

Original publication

DOI

10.7554/eLife.26255

Type

Journal article

Journal

Elife

Publication Date

25/07/2017

Volume

6

Keywords

GWAS, S. pneumoniae, carriage duration, epidemiology, evolutionary biology, genomics, heritability, infectious disease, microbiology, Age Factors, Anti-Bacterial Agents, Carrier State, Child, Preschool, Drug Resistance, Multiple, Bacterial, Female, Genetic Variation, Genome, Bacterial, Genome-Wide Association Study, Genotype, Host-Pathogen Interactions, Humans, Infant, Infant, Newborn, Longitudinal Studies, Male, Markov Chains, Models, Genetic, Nasopharynx, Phylogeny, Serogroup, Streptococcus pneumoniae, Time Factors