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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, *
* Corresponding author
1 The Wellcome Trust Sanger Institute [Cambridge]
2 CAM - University of Cambridge [UK]
3 University of Liverpool
4 MLW - Malawi Liverpool Wellcome Trust Clinical Research Programme
LSTM - Liverpool School of Tropical Medicine, University of Liverpool, Wellcome Trust, University of Malawi
5 NICD - National Institute for Communicable Diseases [Johannesburg]
6 WITS - University of the Witwatersrand [Johannesburg]
7 UCL - University College of London [London]
8 MRC - Medical Research Council Unit The Gambia
9 University of Edinburgh
10 Harvard T.H. Chan School of Public Health
11 University of Nebraska Medical Center
12 IFAIN - International Foundation Against Infectious Diseases in Nigeria
13 CERMES - Centre de Recherche Médicale et Sanitaire (Niamey, Niger)
14 Swiss Tropical and Public Health Institute [Basel]
15 CISM - Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique]
16 Emory University [Atlanta, GA]
17 CDC - Centers for Disease Control and Prevention [Atlanta]
18 University of Warwick [Coventry]
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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https://hal-riip.archives-ouvertes.fr/pasteur-03238211
Contributor : Jean-Marc Collard <>
Submitted on : Thursday, May 27, 2021 - 5:32:43 AM
Last modification on : Thursday, June 10, 2021 - 3:10:33 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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