More Like this

1. The Diverse Antimicrobial Activities of Human Milk Oligosaccharides against Group B Streptococcus

   https://doi.org/10.1002/cbic.202100423  

   Moore, Rebecca E. ; Townsend, Steven D. ; Gaddy, Jennifer A. ( October 2021 , ChemBioChem)

   Streptococcus agalactiaeor Group BStreptococcus(GBS) is a Gram‐positive bacterial pathobiont that is the etiological cause of severe perinatal infections. GBS can colonize the vagina of pregnant patients and invade tissues causing ascending infections of the gravid reproductive tract that lead to adverse outcomes including preterm birth, neonatal sepsis, and maternal or fetal demise. Additionally, transmission of GBS during labor or breastfeeding can also cause invasive infections of neonates and infants. However, human milk has also been shown to have protective effects against infection; a characteristic that is likely derived from antimicrobial and immunomodulatory properties of molecules that comprise human milk. Recent evidence suggests that human milk oligosaccharides (HMOs), short‐chain sugars that comprise 8–20 % of breast milk, have antimicrobial and anti‐biofilm activity against GBS and other bacterial pathogens. Additionally, HMOs have been shown to potentiate the activity of antibiotics against GBS. This review presents the most recent published work that studies the interaction between HMOs and GBS.

    

   more » « less
2. Anti‐biofilm Activity of Human Milk Oligosaccharides in Clinical Strains of Streptococcus agalactiae with Diverse Capsular and Sequence Types

   https://doi.org/10.1002/cbic.202200643  

   Moore, Rebecca E. ; Spicer, Sabrina K. ; Talbert, Julie A. ; Manning, Shannon D. ; Townsend, Steven D. ; Gaddy, Jennifer A. ( February 2023 , ChemBioChem)

   Group BStreptococcus(GBS) is an encapsulated Gram‐positive bacterial pathogen that causes severe perinatal infections. Human milk oligosaccharides (HMOs) are short‐chain sugars that have recently been shown to possess antimicrobial and anti‐biofilm activity against a variety of bacterial pathogens, including GBS. We have expanded these studies to demonstrate that HMOs can inhibit and dismantle biofilm in both invasive and colonizing strains of GBS. A cohort of 30 diverse strains of GBS were analyzed for susceptibility to HMO‐dependent biofilm inhibition or destruction. HMOs were significantly effective at inhibiting biofilm in capsular‐type‐ and sequence‐type‐specific fashion, with significant efficacy in CpsIb, CpsII, CpsIII, CpsV, and CpsVI strains as well as ST‐1, ST‐12, ST‐19, and ST‐23 strains. Interestingly, CpsIa as well as ST‐7 and ST‐17 were not susceptible to the anti‐biofilm activity of HMOs, underscoring the strain‐specific effects of these important antimicrobial molecules against the perinatal pathogenStreptococcus agalactiae.

    

   more » « less
3. Galacto‐Oligosaccharide Supplementation Modulates Pathogen‐Commensal Competition between Streptococcus agalactiae and Streptococcus salivarius

   https://doi.org/10.1002/cbic.202100559  

   Moore, Rebecca E. ; Thomas, Harrison C. ; Manning, Shannon D. ; Gaddy, Jennifer A. ; Townsend, Steven D. ( November 2021 , ChemBioChem)

   The members of the infant microbiome are governed by feeding method (breastmilk vs. formula). Regardless of the source of nutrition, a competitive growth advantage can be provided to commensals through prebiotics – either human milk oligosaccharides (HMOs) or plant oligosaccharides that are supplemented into formula. To characterize how prebiotics modulate commensal – pathogen interactions, we have designed and studied a minimal microbiome where a pathogen,Streptococcus agalactiaeengages with a commensal,Streptococcus salivarius. We discovered that whileS. agalactiaesuppresses the growth ofS. salivariusvia increased lactic acid production, galacto‐oligosaccharides (GOS) supplementation reverses the effect. This result has major implications in characterizing how single species survive in the gut, what niche they occupy, and how they engage with other community members.

    

   more » « less
4. Antibacterial and Anti‐biofilm Activity of the Human Breast Milk Glycoprotein Lactoferrin against Group B Streptococcus

   https://doi.org/10.1002/cbic.202100016  

   Lu, Jacky ; Francis, Jamisha D. ; Guevara, Miriam A. ; Moore, Rebecca E. ; Chambers, Schuyler A. ; Doster, Ryan S. ; Eastman, Alison J. ; Rogers, Lisa M. ; Noble, Kristen N. ; Manning, Shannon D. ; et al ( March 2021 , ChemBioChem)

   Group BStreptococcus(GBS) is an encapsulated Gram‐positive human pathogen that causes invasive infections in pregnant hosts and neonates, as well as immunocompromised individuals. Colonization of the human host requires the ability to adhere to mucosal surfaces and circumnavigate the nutritional challenges and antimicrobial defenses associated with the innate immune response. Biofilm formation is a critical process to facilitate GBS survival and establishment of a replicative niche in the vertebrate host. Previous work has shown that the host responds to GBS infection by producing the innate antimicrobial glycoprotein lactoferrin, which has been implicated in repressing bacterial growth and biofilm formation. Additionally, lactoferrin is highly abundant in human breast milk and could serve a protective role against invasive microbial pathogens. This study demonstrates that human breast milk lactoferrin has antimicrobial and anti‐biofilm activity against GBS and inhibits its adherence to human gestational membranes. Together, these results indicate that human milk lactoferrin could be used as a prebiotic chemotherapeutic strategy to limit the impact of bacterial adherence and biofilm formation on GBS‐associated disease outcomes.

    

   more » « less
5. Substrate and Process Engineering for Biocatalytic Synthesis and Facile Purification of Human Milk Oligosaccharides

   https://doi.org/10.1002/cssc.202102539  

   Bai, Yuanyuan ; Yang, Xiaohong ; Yu, Hai ; Chen, Xi ( February 2022 , ChemSusChem)

   Innovation in process development is essential for applying biocatalysis in industrial and laboratory production of organic compounds, including beneficial carbohydrates such as human milk oligosaccharides (HMOs). HMOs have attracted increasing attention for their potential application as key ingredients in products that can improve human health. To efficiently access HMOs through biocatalysis, a combined substrate and process engineering strategy is developed, namely multistep one‐pot multienzyme (MSOPME) design. The strategy allows access to a pure tagged HMO in a single reactor with a single C18‐cartridge purification process, despite the length of the target. Its efficiency is demonstrated in the high‐yielding (71–91 %) one‐pot synthesis of twenty tagged HMOs (83–155 mg), including long‐chain oligosaccharides with or without fucosylation or sialylation up to nonaoses from a lactoside without the isolation of the intermediate oligosaccharides. Gram‐scale synthesis of an important HMO derivative – tagged lacto‐N‐fucopentaose‐I (LNFP‐I) – proceeds in 84 % yield. Tag removal is carried out in high efficiency (94–97 %) without the need for column purification to produce the desired natural HMOs with a free reducing end. The method can be readily adapted for large‐scale synthesis and automation to allow quick access to HMOs, other glycans, and glycoconjugates.

    

   more » « less