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

Chrispin Chaguza 1, 2, * Marie Yang 3 Jennifer Cornick 3, 4 Mignon Du Plessis 5, 6 Rebecca Gladstone 1 Brenda Kwambana-Adams 7, 8 Stephanie Lo 1 Chinelo Ebruke 8 Gerry Tonkin-Hill 1 Chikondi Peno 4, 9 Madikay Senghore 8, 10 Stephen Obaro 11, 12 Sani Ousmane 13 Gerd Pluschke 14 Jean-Marc Collard 13 Betuel Sigaùque 15 Neil French 3 Keith Klugman 16 Robert Heyderman 4, 7 Lesley Mcgee 17 Martin Antonio 8, 18 Robert Breiman 16 Anne von Gottberg 5, 6 Dean Everett 4, 9 Aras Kadioglu 3 Stephen Bentley 1, 2, *
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.
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Submitted on : Thursday, May 27, 2021 - 5:32:43 AM
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Chrispin Chaguza, Marie Yang, Jennifer Cornick, Mignon Du Plessis, Rebecca Gladstone, et al.. Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism. Communications Biology, Nature Publishing Group, 2020, 3 (1), pp.559. ⟨10.1038/s42003-020-01290-9⟩. ⟨pasteur-03238211⟩

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