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 Bancroft, Archibald Worwui, Ebenezer Foster-Nyarko, Fatima Ceesay, Catherine Okoi, Lesley McGee, Keith P. Klugman, Robert F. Breiman, Michael R. Barer, Richard A. Adegbola, Martín Antonio, Stephen D. Bentley, Brenda Kwambana-Adams
Abstract
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.