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

Chrispin Chaguza, Marie Yang, Jennifer E. Cornick, Mignon du Plessis, Rebecca A. Gladstone, Brenda A. Kwambana-Adams, Stephanie W. Lo, Chinelo Ebruke, Gerry Tonkin-Hill, Chikondi Peno, Madikay Senghore, Stephen K. Obaro, Sani Ousmane, Gerd Pluschke, Jean Marc Collard, Betuel Sigaùque, Neil French, Keith P. Klugman, Robert S. Heyderman, Lesley McGeeMartin Antonio, Robert F. Breiman, Anne von Gottberg, Dean B. Everett, Aras Kadioglu, Stephen D. Bentley

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number559
JournalCommunications biology
Volume3
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)
  • Medicine(all)

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