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.

Management of Infants at Risk for Group B Streptococcal Disease

“…24,56 44,45 Group B streptococci express multiple additional virulence factors, including surface proteins such as the a and b C-proteins that promote adherence and immune evasion, pore-forming toxins such as b-hemolysin and CAMP factor, and secreted proteases such as the C5a peptidase that cleaves complement. 57 Strains vary in their expression of virulence factors, many of which are highly regulated by 2-component regulatory systems. [58][59][60][61][62] The hypervirulent serotype III multilocus sequence type 17 (ST17), for example, is commonly found in cases of GBS meningitis.…”

The Fungal Pathogen Candida albicans Promotes Bladder Colonization of Group B Streptococcus

“…For example, in the elderly, where the incidence of invasive GBS has increased two-to fourfold in the past 20 years, 39% of GBS bacteremia cases are associated with concurrent GBS bacteriuria (Edwards and Baker, 2005). In pregnancy, GBS bacteriuria increases risk for intrapartum fever, chorioamnionitis, preterm delivery, and vertical transmission of the pathogen to the newborn (Patras and Nizet, 2018). Despite these risks associated with GBS bacteriuria, the mechanisms that drive GBS colonization and pathogenesis in the urinary tract remain poorly understood.…”

Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors

“…GBS can successfully adhere to human mucosal cell lines, including vaginal, cervical and airway epithelial cell lines (Patras & Nizet, 2018). Yet, knowledge of the specific host factors that can be targeted by GBS for adhesion is lacking.…”

“…Despite public health interventions, GBS is estimated to cause 410,000 infants infections and 150,000 stillbirths per year (Seale et al, 2017). Cellular adhesion to mucosal surfaces is the first critical step preceding infection (Patras & Nizet, 2018). Bacteria colonization is a multifactorial process that requires expression of adhesins that target extracellular matrix (ECM) constituents and/or host cell receptors (Pietrocola et al, 2018; Shabayek & Spellerberg, 2018).…”

“…The mechanisms underpinning binding to ECM constituents are well-defined, and include targeting fibronectin, laminin and vitronectin (Deng et al, 2019;Spellerberg et al, 1999;Hull et al;Banerjee et al, 2011). In contrast, our knowledge of the mechanisms that GBS utilizes to directly promote host cell adhesion is limited (Patras & Nizet, 2018;Bolduc & Madoff, 2007;Pietrocola et al, 2018). In particular, the host receptors targets of several putative adhesins, including Rib and Sip proteins (Stålhammar-Carlemalm et al, 1993;Brodeur et al, 2000), remain uncharacterized.…”