Mechanisms of group B Streptococcus-mediated preterm birth: lessons learnt from animal models

Abstract

Group B Streptococcus (GBS) is an opportunistic pathogenic bacterium which upon colonization in the female reproductive tract can cause preterm births, fetal injury, and demise. Several determinants for GBS pathogenesis have been explored so far through the studies using animal models ranging from mice to non-human primates. The results from these experimental data have identified outer membrane vesicles, β-hemolysin, hyaluronidase, and Cas9 of GBS as major virulence factors leading to preterm births. Most of these factors drive inflammation through activation of NLRP3 and elevated production of IL1-β. However, the absence of one of the factors from the pathogen reduces but does not completely abolish the pathogenesis of GBS suggesting the involvement of more than one factor in causing preterm birth. This makes further exploration of other virulence factors of GBS pathogenesis important in gaining an insight into the mechanistic basis of GBS-mediated preterm births.

An opportunistic pathogen under stress: how Group B Streptococcus responds to cytotoxic reactive species and conditions of metal ion imbalance to survive

“…Hyaluronidase (HylB) for example, mediates host immune evasion in uterine tissue (Vornhagen et al 2016 ) and dampens inflammatory cascades by degrading proinflammatory hyaluronan fragments that are released during tissue injury. The degraded fragments bind to host toll-like receptor 2 (TLR2) and TLR4 to initiate a weak inflammation cascade and block GBS recognition by receptors to disrupt host immune responses (Kolar et al 2015 , Kurian and Modi 2022 ). Expression of HylB by GBS also limits ROS production and confers resistance to PMNL-mediated killing (Coleman et al 2021 ).…”

Current research update on group B streptococcal infection related to obstetrics and gynecology

“…Regulates immune response and assists bacterial colonization and invasion; helps GBS ascend from vagina to fetus (Liu et al, 2022;Coleman et al, 2021;Kurian and Modi, 2022) Frontiers in Pharmacology frontiersin.org (Shabayek et al, 2018). Additionally, SfbA plays a crucial role in the interaction between GBS and the blood-brain barrier and in the pathogenesis of GBS meningitis.…”

“…This enzyme degrades hyaluronic acid polymers, which are present in the extracellular matrix of human cells, into disaccharide units, disrupting cellular signaling and promoting the expression of inflammatory mediators. It has the capability to break down hyaluronic acid in the connective tissue matrix, disintegrate proteoglycans in connective tissues, and regulate the immune response during colonization and invasion by the bacteria, suppressing the production of reactive oxygen species (ROS) and resisting the action of neutrophils ( Coleman et al, 2021 ; Kurian and Modi, 2022 ). Most importantly, hyaluronidase can breach the barrier between mother and fetus, allowing GBS to ascend from the vagina to the fetus, leading to fatal infections in the fetus ( Liu et al, 2022 ).…”

Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation

“…The high vaginal colonization of S. agalactiae is the main cause of vertical transmission, resulting in invasive infections such as pneumonia and neonatal meningitis ( 125 ). Understanding the pathogenesis of S. agalactiae will allow the development of effective vaccines and therapies against the pathogen ( 126 ). The secretion of IL-1β and IL-18 in human macrophages treated with β-hemolysin from S. agalactiae was associated with NLRP3 inflammasome activation during bacterial infection-mediated fetal death ( 127 ).…”