Genomic adaptation in group B Streptococcus following intrapartum antibiotic prophylaxis and childbirth

Through vaginal colonization, group B Streptococcus (GBS) causes severe outcomes including neonatal sepsis and meningitis. Although intrapartum antibiotic prophylaxis (IAP) has reduced neonatal disease rates, GBS can persist in the genitourinary tract even after antibiotic administration. To determine if IAP selects for genomic signatures that enhance GBS survival and persistence, we compared the isolates from individuals before (prenatal) and after (postpartum) IAP/childbirth. Among 34 of the paired strains from participants with persistent colonization, 31 (91.2%) clustered together in a core gene phylogeny, suggesting colonization with highly similar strains before and after IAP. A core-gene mutation analysis, however, identified mutations in 74% (n = 23) of these 31 postpartum genomes when each genome was compared to its respective prenatal genome from the same individuals. Several strains acquired mutations in the same genes, although two postpartum strains accounted for most of the mutations. These two strains were classified as mutators based on high mutation rates and mutations within DNA repair system genes. Changes in biofilm production were observed in a subset of postpartum strains, which is supported by the presence of point mutations in genes linked to survival and colonization. These findings suggest that exposures encountered during pregnancy and childbirth may select for mutations and phenotypes that promote adaptation and survival in vivo. Enhanced survival in the genitourinary tract can lead to persistent colonization, increasing the likelihood of invasive disease in subsequent pregnancies and in newborns (late-onset infections) following IAP cessation.IMPORTANCEGBS remains a major cause of neonatal sepsis, pneumonia, and meningitis despite the common use of IAP that aims to eradicate maternal colonization, the main risk factor for neonatal disease. Although IAP has reduced the incidence of early-onset neonatal infections, it has had no impact on late-onset infections in babies between 7 days and 3 months of age. Since colonization is intermittent and GBS has been shown to persist in the genitourinary tract despite antibiotic exposure, more research is needed to understand mechanisms of adaptation. By comparing the genomes of GBS strains recovered before (prenatal) and after (postpartum) IAP and childbirth, this study demonstrates how selective pressures shape GBS evolution, favoring traits that promote survival and persistence. Understanding adaptive traits is essential for improving diagnostics, refining prophylaxis strategies, and guiding the development of more effective prevention practices that can reduce the likelihood of GBS transmission to neonates.