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Author Notes:

Chrispin Chaguza, Email: cc19@sanger.ac.uk

Conceptualisation and study design: C.C. and S.D.B. Sample collection, microbiology and molecular work: D.B.E., J.E.C., C.P., C.E., G.P., S.O., R.S.H., N.F., A.V.G., M.D.P., M.A., B.A.K.A., B.S. and J.M.C. Whole-genome sequencing: SDB. Data curation and quality checks: C.C., J.E.C., S.W.L. and R.A.G. Bioinformatics and statistical analysis: C.C. Suggestions on GWAS analysis: G.T. Drafting initial manuscript: C.C. and S.D.B. Discussion and interpretation of the findings, and review and editing of the manuscript: C.C., M.Y., J.E.C., S.W.L., R.A.G., J.E.C., B.S., M.A., C.P., G.T., G.P., M.D.P., M.S., S.O., B.A.K.A., S.O., J.M.C., A.V.G., N.F., R.S.H., R.F.B., L.M., R.F.B., K.P.K., D.B.E., A.K. and S.D.B.

We thank the clinical and laboratory teams at the collaborating institutions, and the sequencing and informatics teams at the Wellcome Sanger Institute. We are also grateful for the insightful feedback on the manuscript provided by Dr. Bernard Beall and Dr. Allen S. Craig at the Centers for Disease Control and Prevention (CDC) in the US.

The authors declare no competing interests.

Subjects:

Research Funding:

This study was funded by the Bill and Melinda Gates Foundation (grant number: OPP1023440 and OPP1034556). C.C., G.T. and S.D.B. were supported by funding from the Joint Programme Initiative for Antimicrobial Resistance (JPIAMR). The contents of this paper are solely the responsibility of the authors and does not necessarily represent the official views of their affiliated institutions and the funding agencies.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biology
  • Multidisciplinary Sciences
  • Life Sciences & Biomedicine - Other Topics
  • Science & Technology - Other Topics
  • STREPTOCOCCUS-PNEUMONIAE SEROTYPE-1
  • AFFINITY LAMININ RECEPTOR
  • INVASIVE-DISEASE
  • SURFACE PROTEIN
  • OUTBREAK
  • MENINGITIS
  • VACCINE
  • VIRUS
  • PSPC
  • CHILDREN

Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism

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Journal Title:

COMMUNICATIONS BIOLOGY

Volume:

Volume 3, Number 1

Publisher:

, Pages 559-559

Type of Work:

Article | Final Publisher PDF

Abstract:

Hyper-virulent Streptococcus pneumoniae serotype 1 strains are endemic in Sub-Saharan Africa and frequently cause lethal meningitis outbreaks. It remains unknown whether genetic variation in serotype 1 strains modulates tropism into cerebrospinal fluid to cause central nervous system (CNS) infections, particularly meningitis. Here, we address this question through a large-scale linear mixed model genome-wide association study of 909 African pneumococcal serotype 1 isolates collected from CNS and non-CNS human samples. By controlling for host age, geography, and strain population structure, we identify genome-wide statistically significant genotype-phenotype associations in surface-exposed choline-binding (P = 5.00 × 10−08) and helicase proteins (P = 1.32 × 10−06) important for invasion, immune evasion and pneumococcal tropism to CNS. The small effect sizes and negligible heritability indicated that causation of CNS infection requires multiple genetic and other factors reflecting a complex and polygenic aetiology. Our findings suggest that certain pathogen genetic variation modulate pneumococcal survival and tropism to CNS tissue, and therefore, virulence for meningitis.

Copyright information:

© The Author(s) 2020

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/).
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