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

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.

eLife digest

Microorganisms live in most parts of our body, including the inside of our nose. Most of the microbes are harmless and can even be beneficial to our health. However, some microbes can cause diseases – although they often go unnoticed, as our immune system can remove them before we show any symptoms. For example, the bacterium Streptococcus pneumoniae can cause diseases such as pneumonia and meningitis, but generally, it lives harmlessly in the nose, and is particularly common in children and the elderly.

The longer the bacteria live in the nose before being killed by the immune system, the more likely they are to be transmitted to another person. The amount of time it takes for the immune system to clear the bacteria depends on various factors, such as the age of the person or the bacterium’s defense mechanism and its genetic material. A particularly important aspect is to what subtype, also known as serotype, a bacterium belongs to, which is characterized by differences in the structure of the sugar coating that surrounds the microbe. However, until now, it was not known how much each of these factors contributes.

Now, Lees et al. have developed a mathematical model to calculate how long the bacteria are carried in the nose before they are cleared away, and compared it with the genomic data of the bacteria. For this, over 14,000 nose swabs from almost 600 children were collected over a two-year period. In their model, Lees et al. calculated that the bacteria’s genetics explained over 60% of the variability in survival time. They also found that the serotype was the most important individual factor that influenced how long a bacterium could survive. The age of the child was less important and only accounted for 5%. In addition, Lees et al. also found that when viruses infected some S. pneumoniae, the bacteria died sooner.

A next step will be to confirm the effect of a viral infection on the bacteria’s survival time in a controlled model system, and also replicate the findings in separate population study.Understanding how long people can carry bacteria and transmit them to others may help to develop new vaccination or treatment strategies to control infections. Moreover, the discovery that viruses can negatively affect how long a bacterium lives, could motivate studies to investigate these findings further.