Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration.

John A Lees,David Goldblatt,Julian Parkhill,Stephen D Bentley,Paul Turner,Nicholas J Croucher,François Nosten,Claudia Turner

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.

Highlights

Streptococcus pneumoniae is a human pathogen that can cause diseases such as pneumonia, otitis media and meningitis
The immune response of mothers to bacterial pathogens is different to children (Marodi, 2006), leading to shorter carriage durations (Gritzfeld et al, 2014)
To estimate carriage duration from the longitudinal swab data we constructed a set of hidden Markov models (HMMs) with hidden states corresponding to whether a child was carrying a serotype at a given time point, and observed states corresponding to whether a positive swab was observed for this serotype at this time point

Summary

Introduction

Streptococcus pneumoniae is a human pathogen that can cause diseases such as pneumonia, otitis media and meningitis. For disease to be caused pneumococci must first transmit to the host, colonise the nasopharynx and cross into a normally sterile site. The pneumococcus spends most of the transmission cycle in the nasopharynx, and so understanding and predicting the amount of time spent in this niche is critical for understanding this bacterium’s epidemiology, and controlling transmission (Abdullahi et al, 2012a; Melegaro et al, 2007). The nasopharynx is a complex niche in which each pneumococcal genotype must tackle a wide range of factors including host immune defence (McCool et al, 2002), other bacterial species (Pericone et al, 2000), and other pneumococcal lineages (Auranen et al, 2010; Cobey and Lipsitch, 2012) in order to maintain the genotype’s population. The average nasopharyngeal duration period is affected by a large number of factors, which may, themselves, interact

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