Julie A Talbert, Sabrina K Spicer, Shannon D Manning, Jennifer A Gaddy, Steven D Townsend
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引用次数: 0
Abstract
Group B Streptococcus (GBS) is an opportunistic bacterium that can cause severe infection during gestation, leading to adverse pregnancy outcomes and neonatal disease. As current treatments only decrease chances of early onset neonatal disease without impacting the risk of chorioamnionitis, preterm birth, or late-onset disease, novel therapeutics are needed. Here, we demonstrate that human milk oligosaccharides (HMOs) positively modulate cocultures of GBS and Lactobacillus spp., common inhabitants of a healthy vaginal microbiome, across in vitro, ex vivo, and in vivo experiments. HMOs shift the total cell population in vitro to favor Lactobacillus, which was qualitatively visualized via scanning electron microscopy. Lactobacillus adherence to EpiVaginal tissues was also increased with HMOs during coinoculation with GBS. Using an in vivo mouse model of reproductive GBS infection, Lactobacillus crispatus and HMOs prevented ascending infection, reducing bacterial burden in both the placenta and fetus. L. crispatus alone reduced the burden in all reproductive tissues tested except the vagina. Together, these results highlight the benefit of pre- and probiotic treatment to potentially reduce GBS colonization during gestation.
期刊介绍:
ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to:
* Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials.
* Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets.
* Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance.
* Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents.
* Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota.
* Small molecule vaccine adjuvants for infectious disease.
* Viral and bacterial biochemistry and molecular biology.