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,
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‐
- NSF-PAR ID:
- 10369823
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- ChemSusChem
- Volume:
- 15
- Issue:
- 9
- ISSN:
- 1864-5631
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract Streptococcus agalactiae engages with a commensal,Streptococcus salivarius . We discovered that whileS. agalactiae suppresses the growth ofS. salivarius via 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
Abstract Streptococcus agalactiae or 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
Abstract Group B
Streptococcus (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 . -
ABSTRACT Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B Streptococcus (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs’ mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs. IMPORTANCE Group B Streptococcus is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.more » « less
-
more » « less
Abstract An orthogonal combination of cationic and radical RAFT polymerizations is used to synthesize bottlebrush polymers using two distinct RAFT agents. Selective consumption of the first RAFT agent is used to control the cationic RAFT polymerization of a vinyl ether monomer bearing a secondary dormant RAFT agent, which subsequently allows side‐chain polymers to be grafted from the pendant RAFT agent by a radical‐mediated RAFT polymerization of a different monomer, thus completing the synthesis of bottlebrush polymers. The high efficiency and selectivity of the cationic and radical RAFT polymerizations allow both polymerizations to be conducted in one‐pot tandem without intermediate purification.
