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Author Notes:

Corresponding authors: E-mails: cc19@sanger.ac.uk; Martin.Antonio@lshtm.ac.uk; sdb@sanger.ac.uk.

C.C., M.A., and S.D.B. conceived the analysis. B.A.K.-A., C.E., M.S., P.-E.T., and M.A. conducted the field studies and sample collection. C.E., P.-E.T., M.S., B.A.K.-A., and M.A. conducted the surveillance and bacteriology work. S.D.B. led the genome sequencing work and supervised data analysis. R.A.G. and S.W.L. performed quality checks and genomic-based serotyping and sequence typing work. C.C. performed data analysis. G.T.-H., N.J.C., and S.D.B. contributed to the discussions on the GWAS analysis. C.C. and S.D.B. wrote the initial draft of the manuscript. C.C., C.E., M.Y., P.-E.T., G.T.-H., M.S., S.W.L., J.E.C., A.W., R.A.G., R.F.B., L.M., K.P.K., D.B.E., G.M., N.J.C., A.R., A.K., B.A.K.-A., M.A., and S.D.B. reviewed the manuscript.

The authors thank the study participants and guardians, microbiology team at the Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene and Tropical Medicine, and the library construction, sequence, and core informatics teams, and the pathogen informatics for their technical support, and the Bentley lab team at the Wellcome Sanger Institute for discussions.

We would also like to thank Dr. Claire Chewapreecha from Mahidol-Oxford Tropical Medicine Research Unit (MORU) for the advice regarding ancestral state reconstruction, and Dr. Yuan Li at the US Centers for Disease Control and Prevention (CDC) for providing feedback on the manuscript.

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Research Funding:

We acknowledge funding from the MRC The Gambia @LSHTM and the Bill and Melinda Gates Foundation (grant numbers: OPP1023440 and OPP1034556), the Joint Programme Initiative for Antimicrobial Resistance (JPIAMR) (grant no. MR/R003076/1), and Wellcome Trust (2016–2021 core award grant no. 206194).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Evolutionary Biology
  • Genetics & Heredity
  • Streptococcus pneumoniae
  • genome-wide association study
  • bacterial genomics
  • genomic epidemiology
  • pathogenicity
  • invasiveness
  • STREPTOCOCCUS-PNEUMONIAE
  • NEISSERIA-MENINGITIDIS
  • WIDE ASSOCIATION
  • VIRULENCE
  • COLONIZATION
  • EPIDEMIOLOGY
  • ACTIVATION
  • OUTBREAK
  • CHILDREN
  • SEQUENCE

Comparative Genomics of Disease and Carriage Serotype 1 Pneumococci

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Journal Title:

GENOME BIOLOGY AND EVOLUTION

Volume:

Volume 14, Number 4

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Type of Work:

Article | Final Publisher PDF

Abstract:

The isolation of Streptococcus pneumoniae serotypes in systemic tissues of patients with invasive disease versus the nasopharynx of healthy individuals with asymptomatic carriage varies widely. Some serotypes are hyper-invasive, particularly serotype 1, but the underlying genetics remain poorly understood due to the rarity of carriage isolates, reducing the power of comparison with invasive isolates. Here, we use a well-controlled genome-wide association study to search for genetic variation associated with invasiveness of serotype 1 pneumococci from a serotype 1 endemic setting in Africa. We found no consensus evidence that certain genomic variation is overrepresented among isolates from patients with invasive disease than asymptomatic carriage. Overall, the genomic variation explained negligible phenotypic variability, suggesting a minimal effect on the disease status. Furthermore, changes in lineage distribution were seen with lineages replacing each other over time, highlighting the importance of continued pathogen surveillance. Our findings suggest that the hyper-invasiveness is an intrinsic property of the serotype 1 strains, not specific for a "disease-associated"subpopulation disproportionately harboring unique genomic variation.

Copyright information:

© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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