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.
https://hal-riip.archives-ouvertes.fr/pasteur-03238211 Contributor : Jean-Marc CollardConnect in order to contact the contributor Submitted on : Thursday, May 27, 2021 - 5:32:43 AM Last modification on : Wednesday, November 24, 2021 - 9:54:21 AM Long-term archiving on: : Saturday, August 28, 2021 - 6:08:04 PM
Chrispin Chaguza, Marie yang, Jennifer E. Cornick, Mignon Du Plessis, Rebecca A. 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⟩