Interspecies Interactions within the Host: the Social Network of Group B Streptococcus

Abstract

Group B Streptococcus (GBS) is a pervasive neonatal pathogen accounting for a combined half a million deaths and stillbirths annually. The most common source of fetal or neonatal GBS exposure is the maternal microbiota. GBS asymptomatically colonizes the gastrointestinal and vaginal mucosa of 1 in 5 individuals globally, although its precise role in these niches is not well understood. To prevent vertical transmission, broad-spectrum antibiotics are administered to GBS-positive mothers during labor in many countries. Although antibiotics have significantly reduced GBS early-onset neonatal disease, there are several unintended consequences, including an altered neonatal microbiota and increased risk for other microbial infections. Additionally, the incidence of late-onset GBS neonatal disease remains unaffected and has sparked an emerging hypothesis that GBS-microbe interactions in developing neonatal gut microbiota may be directly involved in this disease process. This review summarizes our current understanding of GBS interactions with other resident microbes at the mucosal surface from multiple angles, including clinical association studies, agriculture and aquaculture observations, and experimental animal model systems. We also include a comprehensive review of in vitro findings of GBS interactions with other bacterial and fungal microbes, both commensal and pathogenic, along with newly established animal models of GBS vaginal colonization and in utero or neonatal infection. Finally, we provide a perspective on emerging areas of research and current strategies to design microbe-targeting prebiotic or probiotic therapeutic intervention strategies to prevent GBS disease in vulnerable populations.

Keywords: Streptococcus agalactiae; group B Streptococcus; microbe-microbe interactions; probiotic; vaginal microbiota.

FIG 1

Social network of group B Streptococcus: mechanisms of negative (antagonistic) and positive (synergistic) GBS-microbe interactions. The network is ordered clockwise from the lower left. Streptococcus salivarius K12 produces salivaricin A and B to inhibit GBS growth in vitro and reduce GBS vaginal colonization in vivo (206). Lactic acid production by Lactobacillus spp. reduces pH and inhibits GBS growth in vitro (220, 226, 227). Multiple Lactobacillus spp. produce bacteriocin-like inhibitory substances (BLIS) that elicit bactericidal or inhibitory activity. Examples include L. salivarius CRL 1328 salivaricin (221), a L. acidophilus KS400 bacteriocin (222), an L. fermentum CS57 bacteriocin-like substance (218), and synergistic activity of bacteriocins from L. fermentum L23 and L. rhamnosus L60 (223, 224). GBS antigen I/II family adhesins BspA and BspC facilitate GBS interactions with Candida albicans, in part through hypha-specific ALS3, and promote binding of both organisms to the vaginal epithelium (201, 202). GBS supernatant increases S. aureus expression of tst, the gene encoding toxic shock syndrome toxin-1 (TSST-1), in vitro (145).