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

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Chaguza, Chrispin ORCID: 0000-0002-2108-1757, Yang, Marie, Cornick, Jennifer E, du Plessis, Mignon, Gladstone, Rebecca A, Kwambana-Adams, Brenda A, Lo, Stephanie W, Ebruke, Chinelo, Tonkin-Hill, Gerry, Peno, Chikondi et al (show 16 more authors) , Senghore, Madikay, Obaro, Stephen K, Ousmane, Sani, Pluschke, Gerd, Collard, Jean-Marc, Sigauque, Betuel, French, Neil ORCID: 0000-0003-4814-8293, Klugman, Keith P, Heyderman, Robert S, McGee, Lesley, Antonio, Martin, Breiman, Robert F, von Gottberg, Anne, Everett, Dean B, Kadioglu, Aras ORCID: 0000-0003-1137-6321 and Bentley, Stephen D (2020) Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism. COMMUNICATIONS BIOLOGY, 3 (1). 559-. ISSN 2399-3642, 2399-3642

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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.

Item Type:	Article
Uncontrolled Keywords:	Central Nervous System, Humans, Streptococcus pneumoniae, Meningitis, Pneumococcal, Sequence Analysis, DNA, Phylogeny, Polymorphism, Single Nucleotide, Adolescent, Child, Child, Preschool, Infant, Genetic Variation, Genome-Wide Association Study, Viral Tropism
Depositing User:	Symplectic Admin
Date Deposited:	09 Oct 2020 10:55
Last Modified:	07 Dec 2024 10:19
DOI:	10.1038/s42003-020-01290-9
Open Access URL:	https://www.nature.com/articles/s42003-020-01290-9...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3103882