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

Chaguza, Chrispin; 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; +16 more... Senghore, Madikay; Obaro, Stephen K; Ousmane, Sani; Pluschke, Gerd; Collard, Jean-Marc; Sigaùque, Betuel; French, Neil; Klugman, Keith P; Heyderman, Robert S; McGee, Lesley; Antonio, Martin; Breiman, Robert F; von Gottberg, Anne; Everett, Dean B; Kadioglu, Aras; 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 DOI: https://doi.org/10.1038/s42003-020-01290-9

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.

Additional Information

Item Type	Article
Faculty and Department	MRC Gambia > GM-Vaccinology Theme
Research Centre	Centre for Epidemic Preparedness and Response
PubMed ID	33033372
Elements ID	151954