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.
Original language | English |
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Article number | 559 |
Number of pages | 12 |
Journal | Communications Biology |
Volume | 3 |
Issue number | 1 |
DOIs | |
Publication status | Published - 8 Oct 2020 |
Keywords
- Adolescent
- Central Nervous System/microbiology
- Child
- Child, Preschool
- Genetic Variation/genetics
- Genome-Wide Association Study
- Humans
- Infant
- Meningitis, Pneumococcal/microbiology
- Phylogeny
- Polymorphism, Single Nucleotide
- Sequence Analysis, DNA
- Streptococcus pneumoniae/genetics
- Viral Tropism/genetics