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)
(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
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<sup>-08</sup>) and helicase proteins (P = 1.32 × 10<sup>-06</sup>) 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 |
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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: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3103882 |