| dc.description.abstract | Streptococcus agalactiae (Group B Streptococcus, GBS) is an opportunistic bacterium that is commonly isolated from the female gastrointestinal and reproductive tracts. GBS colonization of the rectovaginal mucosa during pregnancy puts the infant at risk for preterm premature rupture of the membranes (PPROM, i.e., the water breaking), preterm birth, stillbirth, maternal sepsis, chorioamnionitis, severe invasive disease, or neonatal mortality. As maternal colonization is the primary route for transmission during labor and delivery, intrapartum antibiotic prophylaxis treatment (IAP) strategies are in place to reduce the risk for transmission. However, in addition to contributing to antibiotic resistance evolution, this strategy does not prevent ascending infection, or late-onset GBS infections. In response to this urgent need to develop novel therapeutics, we have explored human milk oligosaccharides (HMOs), a group of complex sugars only present in breast milk, for their ability to potentiate the activity of select antibiotics against GBS. We hypothesized HMOs permeabilize the cell membrane, which was validated through untargeted metabolomic analyses. Additionally, we investigated their ability to prevent biofilms, an essential virulence factor linked to the pathogenesis of opportunistic bacteria, contributing to multi-drug resistance and increased rates of morbidity and mortality. In our work, we uncovered that HMOs display potent antimicrobial and anti-biofilm activity against GBS in vitro, inhibit GBS adherence and biofilm formation on gestational tissues collected from healthy, term, non-laboring C-section placenta, and to EpiVaginal™ human organoid tissue. HMOs also significantly reduced ascending infection in the mouse model. These results have huge implications on reducing the incidences GBS colonization and disease progression. | |
