Group B Streptococcal Maternal Colonization and Neonatal Disease: Molecular Mechanisms and Preventative Approaches

Abstract

Group B Streptococcus (GBS) colonizes the gastrointestinal and vaginal epithelium of a significant percentage of healthy women, with potential for ascending intrauterine infection or transmission during parturition, creating a risk of serious disease in the vulnerable newborn. This review highlights new insights on the bacterial virulence determinants, host immune responses, and microbiome interactions that underpin GBS vaginal colonization, the proximal step in newborn infectious disease pathogenesis. From the pathogen perspective, the function GBS adhesins and biofilms, β-hemolysin/cytolysin toxin, immune resistance factors, sialic acid mimicry, and two-component transcriptional regulatory systems are reviewed. From the host standpoint, pathogen recognition, cytokine responses, and the vaginal mucosal and placental immunity to the pathogen are detailed. Finally, the rationale, efficacy, and potential unintended consequences of current universal recommended intrapartum antibiotic prophylaxis are considered, with updates on new developments toward a GBS vaccine or alternative approaches to reducing vaginal colonization.

Keywords: group B Streptococcus; intrapartum antibiotic prophylaxis; neonatal sepsis; postpartum disease; vaginal colonization; virulence factors.

Figure 1

Host and bacterial factors contributing to group B Streptococcus (GBS) vaginal colonization. Within the vaginal tract, GBS interacts with other vaginal flora. Lactobacillus and GBS both possess antagonistic activity against each other, likely through production of antimicrobial peptides and niche competition. GBS produces countermeasures such as the protease NSR, which degrades the lantibiotic Nisin produced by Lactococcus. Other flora, such as C. albicans, facilitate GBS vaginal colonization in part through the GBS adhesion BspA. GBS binds to host vaginal epithelial cells and extracellular matrix proteins through surface adhesins including pili, Srr-1 and Srr-2, BsaB, BspA, and BibA. Upon interaction with the epithelium, GBS elicits host cytokine responses such as IL-1β, IL-8, CXCL1, and CXCL2, the latter two of which can be degraded by the serine protease CspA. The vaginal epithelium can also generate antimicrobial peptides, such as LL-37 or β-defensins, which GBS deflects with lipoteichoic acid-anchored d-alanine, or possibly degrades through yet unidentified peptidases. GBS further thwarts innate immune mechanisms by blocking capsular deposition of C3b or through degradation of C5a via ScpB. GBS uses multiple two-component systems to sense environmental conditions and regulate virulence and survival factors via response regulators such as CovR and CiaR.