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

• Type of Material: Article
• Authors: Chrispin Chaguza, Wellcome Sanger Institute; Madikay Senghore, London School of Hygiene & Tropical Medicine; Ebrima Bojang, London School of Hygiene & Tropical Medicine; Rebecca A. Gladstone, Wellcome Sanger Institute; Stephanie W. Lo, Wellcome Sanger Institute; Peggy-Estelle Tientcheu, London School of Hygiene & Tropical Medicine; Rowan E. Bancroft, London School of Hygiene & Tropical Medicine; Archibald Worwui, London School of Hygiene & Tropical Medicine; Ebenezer Foster-Nyarko, London School of Hygiene & Tropical Medicine; Fatima Ceesay, London School of Hygiene & Tropical Medicine; Catherine Okoi, London School of Hygiene & Tropical Medicine; Lesley McGee, Centers for Disease Control and Prevention; Keith Klugman, Emory University; Robert Breiman, Emory University; Michael R. Barer, University of Leicester; Richard A. Adegbola, RAMBICON Immunisation & Global Health Consulting; Martin Antonio, London School of Hygiene & Tropical Medicine; Stephen D. Bentley, Wellcome Sanger Institute; Brenda A. Kwambana-Adams, London School of Hygiene & Tropical Medicine
• Language: English
• Date: 2020-07-10
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-020-17327-w
• Title of Journal or Parent Work: Nature Communications
• Volume: 11
• Issue: 1
• Start Page: 3442
• End Page: 3442
• Grant/Funding Information: C.C. and S.D.B. were funded by the Joint Programme Initiative for Antimicrobial Resistance (JPIAMR).; The study was funded by the Medical Research Council (MRC) Unit The Gambia at London School of Hygiene and Tropical Medicine and the Bill and Melinda Gates Foundation (award no. OPP1034556 to K.P.K., R.F.B., L.M.G. and S.D.B.).
• Keywords: Sequence; Pneumococcal disease; Science & Technology; Kilifi district; Evolution; Resistance; Serotypes; Multidisciplinary Sciences; Children; Nasopharyngeal carriage; Identification; Clones; Science & Technology - Other Topics
• Research Categories: Biology, Microbiology; Health Sciences, Public Health; Health Sciences, Immunology; Biology, Parasitology

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.