%0 Journal Article %T Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism %+ The Wellcome Trust Sanger Institute [Cambridge] %+ University of Cambridge [UK] (CAM) %+ University of Liverpool %+ Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) %+ National Institute for Communicable Diseases [Johannesburg] (NICD) %+ University of the Witwatersrand [Johannesburg] (WITS) %+ University College of London [London] (UCL) %+ Medical Research Council Unit The Gambia (MRC) %+ University of Edinburgh %+ Harvard T.H. Chan School of Public Health %+ University of Nebraska Medical Center %+ International Foundation Against Infectious Diseases in Nigeria (IFAIN) %+ Centre de Recherche Médicale et Sanitaire (Niamey, Niger) (CERMES) %+ Swiss Tropical and Public Health Institute [Basel] %+ Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique] (CISM) %+ Emory University [Atlanta, GA] %+ Centers for Disease Control and Prevention [Atlanta] (CDC) %+ University of Warwick [Coventry] %A Chaguza, Chrispin %A Yang, Marie %A Cornick, Jennifer, E. %A Du Plessis, Mignon %A Gladstone, Rebecca, A. %A Kwambana-Adams, Brenda, A. %A Lo, Stephanie, W. %A Ebruke, Chinelo %A Tonkin-Hill, Gerry %A Peno, Chikondi %A Senghore, Madikay %A Obaro, Stephen, K. %A Ousmane, Sani %A Pluschke, Gerd %A Collard, Jean-Marc %A Sigaùque, Betuel %A French, Neil %A Klugman, Keith, P. %A Heyderman, Robert, S. %A Mcgee, Lesley %A Antonio, Martin %A Breiman, Robert, F. %A von Gottberg, Anne %A Everett, Dean, B. %A Kadioglu, Aras %A Bentley, Stephen, D. %Z This study was funded by the Bill and Melinda Gates Foundation (grant number: OPP1023440 and OPP1034556). C.C., G.T. and S.D.B. were supported by funding from the Joint Programme Initiative for Antimicrobial Resistance (JPIAMR). %< avec comité de lecture %@ 2399-3642 %J Communications Biology %I Nature Publishing Group %V 3 %N 1 %P 559 %8 2020-10-08 %D 2020 %R 10.1038/s42003-020-01290-9 %M 33033372 %Z Life Sciences [q-bio]/Human health and pathology/Infectious diseases %Z Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology %Z Life Sciences [q-bio]/Santé publique et épidémiologieJournal articles %X 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. %G English %2 https://riip.hal.science/pasteur-03238211/document %2 https://riip.hal.science/pasteur-03238211/file/s42003-020-01290-9.pdf %L pasteur-03238211 %U https://riip.hal.science/pasteur-03238211 %~ RIIP %~ SANTE_PUB_INSERM %~ RIIP_CERMES