Abstract
Populations of Streptococcus pneumoniae (SP) are typically structured into groups of closely related organisms or lineages, but it is not clear whether they are maintained by selection or neutral processes. Here, we attempt to address this question by applying a machine learning technique to SP whole genomes. Our results indicate that lineages evolved through immune selection on the groEL chaperone protein. The groEL protein is part of the groESL operon and enables a large range of proteins to fold correctly within the physical environment of the nasopharynx, thereby explaining why lineage structure is so stable within SP despite high levels of genetic transfer. SP is also antigenically diverse, exhibiting a variety of distinct capsular serotypes. Associations exist between lineage and capsular serotype but these can be easily perturbed, such as by vaccination. Overall, our analyses indicate that the evolution of SP can be conceptualized as the rearrangement of modular functional units occurring on several different timescales under different pressures: some patterns have locked in early (such as the epistatic interactions between groESL and a constellation of other genes) and preserve the differentiation of lineages, while others (such as the associations between capsular serotype and lineage) remain in continuous flux.
Highlights
Streptococcus pneumoniae is a gram-positive bacterial pathogen which, commonly carried asymptomatically in the nasopharynx, can cause pneumonia, meningitis, septicemia and bacteremia in the young, elderly and immuno-compromised, being responsible for about 11% of worldwide deaths in children under 5 years of age[1, 2]
We attempt to elucidate potential drivers of lineage structure by applying a machine learning technique known as the Random Forest Algorithm (RFA) to a dataset containing 616 whole genomes of S. pneumoniae collected in Massachusetts (USA) between 2001 and 20078
In this paper, was to test the hypothesis that the stratification of pneumococcal populations into distinct sequence clusters or lineages occurred through neutral processes, with serotype diversity being superimposed upon the ensuing clonal framework to minimize antigenic interference between lineages
Summary
Streptococcus pneumoniae (the pneumococcus) is a gram-positive bacterial pathogen which, commonly carried asymptomatically in the nasopharynx, can cause pneumonia, meningitis, septicemia and bacteremia in the young, elderly and immuno-compromised, being responsible for about 11% of worldwide deaths in children under 5 years of age[1, 2]. Reductions in disease rates have been achieved by the deployment of the PCV7 vaccine targeting 7 of the most common serotypes in invasive disease, and more recently through the use of PCV13 which extends coverage to an additional 6 serotypes This has been accompanied by an increase in the frequency of non-vaccine serotypes in many parts of the world, likely due to the removal of competition from vaccine serotypes[4]. Like many other bacterial pathogen populations, S. pneumoniae may be organised into a number of so-called clonal complexes on the basis of allelic diversity at selected housekeeping loci (determining Multilocus Sequence Type5, 6,). The maintenance of discrete major lineages, and their associations with distinct serotypes and clonal complexes, is hard to ascribe to purely neutral processes, given the high rate of genetic exchange in these pathogen populations[12, 13]. The output of an RFA is composed both of the classification success rates of the response variable and a ranking of the predictor variables quantifying their relative role in the classification process
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