Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation

Chrispin Chaguza, Madikay Senghore, Ebrima Bojang, Rebecca A Gladstone, Stephanie W Lo, Peggy-Estelle Tientcheu, Rowan E Bancroft, Archibald Worwui, Ebenezer Foster-Nyarko, Fatima Ceesay, Catherine Okoi, Lesley McGee, Keith P Klugman, Robert F Breiman, Michael R Barer, Richard A Adegbola, Martin Antonio, Stephen D Bentley, Brenda A Kwambana-Adams

Research output: Contribution to journalArticlepeer-review

27 Citations (SciVal)


Genomic evolution, transmission and pathogenesis of Streptococcus pneumoniae, an opportunistic human-adapted pathogen, is driven principally by nasopharyngeal carriage. However, little is known about genomic changes during natural colonisation. Here, we use whole-genome sequencing to investigate within-host microevolution of naturally carried pneumococci in ninety-eight infants intensively sampled sequentially from birth until twelve months in a high-carriage African setting. We show that neutral evolution and nucleotide substitution rates up to forty-fold faster than observed over longer timescales in S. pneumoniae and other bacteria drives high within-host pneumococcal genetic diversity. Highly divergent co-existing strain variants emerge during colonisation episodes through real-time intra-host homologous recombination while the rest are co-transmitted or acquired independently during multiple colonisation episodes. Genic and intergenic parallel evolution occur particularly in antibiotic resistance, immune evasion and epithelial adhesion genes. Our findings suggest that within-host microevolution is rapid and adaptive during natural colonisation.

Original languageEnglish
Pages (from-to)3442
JournalNature Communications
Issue number1
Publication statusPublished - 10 Jul 2020


  • Evolution, Molecular
  • Genetics
  • Genome, Bacterial/genetics
  • Humans
  • Pneumococcal Infections/genetics
  • Streptococcus pneumoniae/genetics
  • Whole Genome Sequencing


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