Chaguza, C;
Yang, M;
Cornick, JE;
du Plessis, M;
Gladstone, RA;
Kwambana-Adams, BA;
Lo, SW;
... Bentley, SD; + view all
(2020)
Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism.
Communications Biology
, 3
(1)
, Article 559. 10.1038/s42003-020-01290-9.
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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.
| Type: | Article |
|---|---|
| Title: | Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s42003-020-01290-9 |
| Publisher version: | https://doi.org/10.1038/s42003-020-01290-9 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Bacterial evolution, Bacterial genomics, Comparative genomics, Genetic variation, Genome-wide association studies |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10113212 |
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