Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion

被引:19
作者
Chaguza, Chrispin [1 ,2 ]
Jamrozy, Dorota [1 ]
Bijlsma, Merijn W. [3 ]
Kuijpers, Taco W. [4 ,5 ]
van de Beek, Diederik [3 ]
van der Ende, Arie [6 ,7 ]
Bentley, Stephen D. [1 ]
机构
[1] Wellcome Sanger Inst, Parasites & Microbes Programme, Wellcome Genome Campus, Cambridge, England
[2] Yale Univ, Dept Epidemiol Microbial Dis, Yale Sch Publ Hlth, New Haven, CT 06520 USA
[3] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Neurol, Amsterdam Neurosci, Amsterdam, Netherlands
[4] Univ Amsterdam, Sanquin Res & Landsteiner Lab, Dept Immunopathol, Acad Med Ctr, Amsterdam, Netherlands
[5] Univ Amsterdam, Emma Childrens Hosp, Dept Paediat Haematol Immunol & Infect Dis, Med Ctr, Amsterdam, Netherlands
[6] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Microbiol, Amsterdam Infect & Immun, Amsterdam, Netherlands
[7] Amsterdam Univ Med Ctr, Ctr Infect & Immun Amsterdam, Netherlands Reference Lab Bacterial Meningitis, Amsterdam, Netherlands
基金
英国惠康基金;
关键词
EPIDEMIOLOGY; MENINGITIS; CAPSULE; PROTEIN; POLYSACCHARIDE; NETHERLANDS; FIBRINOGEN; NEWBORNS; INFANT;
D O I
10.1038/s41467-022-31858-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Group B Streptococcus (GBS) causes neonatal disease and mortality worldwide. Here, the authors use genome-wide association analyses to identify bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease.
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页数:13
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