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

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Yang, Marie 
Cornick, Jennifer E. 
Gladstone, Rebecca A. 


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.


Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)


Article, /631/326/41/2529, /631/181/457/649, /631/208/205/2138, /631/208/212/748, /631/326/41/2530, /45, /45/43, /45/23, article

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Communications Biology

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Nature Publishing Group UK
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) (OPP1023440, OPP1034556)