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

Chaguza, Chrispin and Yang, Marie and Cornick, Jennifer E. and du Plessis, Mignon and Gladstone, Rebecca A. and Kwambana-Adams, Brenda A. and Lo, Stephanie W. and Ebruke, Chinelo and Tonkin-Hill, Gerry and Peno, Chikondi and Senghore, Madikay and Obaro, Stephen K. and Ousmane, Sani and Pluschke, Gerd and Collard, Jean-Marc and Sigaùque, Betuel and French, Neil and Klugman, Keith P. and Heyderman, Robert S. and McGee, Lesley and Antonio, Martin and Breiman, Robert F. and von Gottberg, Anne and Everett, Dean B. and Kadioglu, Aras 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. p. 559.

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Molecular Immunology (Pluschke)
UniBasel Contributors:Pluschke, Gerd
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2399-3642
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
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Last Modified:19 Dec 2022 10:02
Deposited On:19 Dec 2022 10:02

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