TY - JOUR
T1 - Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion
AU - Chaguza, Chrispin
AU - Jamrozy, Dorota
AU - Bijlsma, Merijn W.
AU - Kuijpers, Taco W.
AU - van de Beek, Diederik
AU - van der Ende, Arie
AU - Bentley, Stephen D.
N1 - Funding Information: The authors would like to thank the study participants and guardians, the clinical and laboratory staff who collected and processed the samples at various laboratories in the Netherlands, and the sequencing, core, and pathogen teams, and the Bentley lab at the Wellcome Sanger Institute for their support and feedback on the genomic analysis. We would also like to thank Dr. John Lees at European Bioinformatics Institute for providing advice on the GWAS. The study was funded by the Meningitis Research Foundation Project grant 1502.0 (A.v.d.E.), Wellcome Trust grant 098051 (D.J., S.D.B.), Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici 918.19.627 (D.v.d.B.), Amsterdam Medical Centre Innovation grant (D.v.d.B.), and the Bill and Melinda Gates Foundation grant for the Juno project (SDB) [ https://www.gbsgen.net/ ]. C.C. and S.D.B. were supported by funding from the Joint Initiative for Antimicrobial Resistance (JPIAMR) grant no. MR/R003076/1 (S.D.B.), the Bill and Melinda Gates Foundation grant number OPP1034556 (S.D.B.), and Wellcome Trust (2016–2021 core award grant no. 206194). Funding Information: The authors would like to thank the study participants and guardians, the clinical and laboratory staff who collected and processed the samples at various laboratories in the Netherlands, and the sequencing, core, and pathogen teams, and the Bentley lab at the Wellcome Sanger Institute for their support and feedback on the genomic analysis. We would also like to thank Dr. John Lees at European Bioinformatics Institute for providing advice on the GWAS. The study was funded by the Meningitis Research Foundation Project grant 1502.0 (A.v.d.E.), Wellcome Trust grant 098051 (D.J., S.D.B.), Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici 918.19.627 (D.v.d.B.), Amsterdam Medical Centre Innovation grant (D.v.d.B.), and the Bill and Melinda Gates Foundation grant for the Juno project (SDB) [https://www.gbsgen.net/]. C.C. and S.D.B. were supported by funding from the Joint Initiative for Antimicrobial Resistance (JPIAMR) grant no. MR/R003076/1 (S.D.B.), the Bill and Melinda Gates Foundation grant number OPP1034556 (S.D.B.), and Wellcome Trust (2016–2021 core award grant no. 206194). Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Group B Streptococcus (GBS), or Streptococcus agalactiae, is a pathogen that causes preterm births, stillbirths, and acute invasive neonatal disease burden and mortality. Here, we investigate bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease. We carry out a genome-wide association study (GWAS) of 1,338 GBS isolates from newborns with acute invasive disease; the isolates had been collected annually, for 30 years, through a national bacterial surveillance program in the Netherlands. After controlling for the population structure, we identify genetic variation within noncoding and coding regions, particularly the capsule biosynthesis locus, statistically associated with neonatal GBS disease onset time and meningeal invasion. Our findings highlight the impact of integrating microbial population genomics and clinical pathogen surveillance, and demonstrate the effect of GBS genetics on disease pathogenesis in neonates and infants.
AB - Group B Streptococcus (GBS), or Streptococcus agalactiae, is a pathogen that causes preterm births, stillbirths, and acute invasive neonatal disease burden and mortality. Here, we investigate bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease. We carry out a genome-wide association study (GWAS) of 1,338 GBS isolates from newborns with acute invasive disease; the isolates had been collected annually, for 30 years, through a national bacterial surveillance program in the Netherlands. After controlling for the population structure, we identify genetic variation within noncoding and coding regions, particularly the capsule biosynthesis locus, statistically associated with neonatal GBS disease onset time and meningeal invasion. Our findings highlight the impact of integrating microbial population genomics and clinical pathogen surveillance, and demonstrate the effect of GBS genetics on disease pathogenesis in neonates and infants.
UR - http://www.scopus.com/inward/record.url?scp=85134622889&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-022-31858-4
DO - https://doi.org/10.1038/s41467-022-31858-4
M3 - Article
C2 - 35864107
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4215
ER -