Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism
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Cornick, Jennifer E.
Gladstone, Rebecca A.
Kwambana-Adams, Brenda A.
Lo, Stephanie W.
Obaro, Stephen K.
Klugman, Keith P.
Heyderman, Robert S.
Breiman, Robert F.
von Gottberg, Anne
Everett, Dean B.
Nature Publishing Group UK
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Chaguza, C., Yang, M., Cornick, J. E., du Plessis, M., Gladstone, R. A., Kwambana-Adams, B. A., Lo, S. W., et al. (2020). Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism. Communications Biology, 3 (1)https://doi.org/10.1038/s42003-020-01290-9
Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
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.
Article, /631/326/41/2529, /631/181/457/649, /631/208/205/2138, /631/208/212/748, /631/326/41/2530, /45, /45/43, /45/23, article
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) (OPP1023440, OPP1034556)
External DOI: https://doi.org/10.1038/s42003-020-01290-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329157