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Frequent recombination of pneumococcal capsule highlights future risks of emergence of novel serotypes

View ORCID ProfileRafał J. Mostowy, View ORCID ProfileNicholas J. Croucher, View ORCID ProfileNicola De Maio, View ORCID ProfileClaire Chewapreecha, View ORCID ProfileSusannah J. Salter, View ORCID ProfilePaul Turner, David M. Aanensen, Stephen D. Bentley, View ORCID ProfileXavier Didelot, View ORCID ProfileChristophe Fraser
doi: https://doi.org/10.1101/098335
Rafał J. Mostowy
1Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, W2 1PG London, UK
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  • For correspondence: r.mostowy@imperial.ac.uk
Nicholas J. Croucher
1Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, W2 1PG London, UK
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Nicola De Maio
2Nuffield Department of Medicine, University of Oxford, Oxford, UK
3Institute for Emerging Infections, Oxford Martin School, Oxford, UK
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Claire Chewapreecha
4Department of Medicine, University of Cambridge, Cambridge, UK
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Susannah J. Salter
5The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
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Paul Turner
6Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
7Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
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David M. Aanensen
1Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, W2 1PG London, UK
8Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK
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Stephen D. Bentley
5The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
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Xavier Didelot
1Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, W2 1PG London, UK
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Christophe Fraser
1Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, W2 1PG London, UK
9Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK
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Abstract

Capsular diversity of Streptococcus pneumoniae constitutes a major obstacle in eliminating the pneumococcal disease. Such diversity is genetically encoded by almost 100 variants of the capsule polysaccharide locus (cps). However, the evolutionary dynamics of the capsule – the target of the currently used vaccines – remains not fully understood. Here, using genetic data from 4,469 bacterial isolates, we found cps to be an evolutionary hotspot with elevated substitution and recombination rates. These rates were a consequence of altered selection at this locus, supporting the hypothesis that the capsule has an increased potential to generate novel diversity compared to the rest of the genome. Analysis of twelve serogroups revealed their complex evolutionary history, which was principally driven by recombination with other serogroups and other streptococci. We observed significant variation in recombination rates between different serogroups. This variation could only be partially explained by the lineage-specific recombination rate, the remaining factors being likely driven by serogroup-specific ecology and epidemiology. Finally, we discovered two previously unobserved mosaic serotypes in the densely sampled collection from Mae La, Thailand, here termed 10X and 21X. Our results thus emphasise the strong adaptive potential of the bacterium by its ability to generate novel serotypes by recombination.

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Posted January 04, 2017.
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Frequent recombination of pneumococcal capsule highlights future risks of emergence of novel serotypes
Rafał J. Mostowy, Nicholas J. Croucher, Nicola De Maio, Claire Chewapreecha, Susannah J. Salter, Paul Turner, David M. Aanensen, Stephen D. Bentley, Xavier Didelot, Christophe Fraser
bioRxiv 098335; doi: https://doi.org/10.1101/098335
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Frequent recombination of pneumococcal capsule highlights future risks of emergence of novel serotypes
Rafał J. Mostowy, Nicholas J. Croucher, Nicola De Maio, Claire Chewapreecha, Susannah J. Salter, Paul Turner, David M. Aanensen, Stephen D. Bentley, Xavier Didelot, Christophe Fraser
bioRxiv 098335; doi: https://doi.org/10.1101/098335

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