Antimicrobial and Antibiofilm Activity of Human Milk Oligosaccharides against Streptococcus agalactiae, Staphylococcus aureus, and Acinetobacter baumannii

Ackerman, Dorothy L.; Craft, Kelly M.; Doster, Ryan S.; Weitkamp, Jörn-Hendrik; Aronoff, David M.; Gaddy, Jennifer A.; Townsend, Steven D.

doi:10.1021/acsinfecdis.7b00183

Cited by 82 publications

(104 citation statements)

References 52 publications

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“…GBS is a major cause of infection of the fetal membranes (chorioamnionitis), which can lead to neonatal sepsis, preterm birth, and still birth. HMOs also showed antibacterial activity against Acinetobacter buamannii which can cause blood and urinary tract infections as well as antibiofilm activity against methicillin-resistant Staphylococcus aureus [110][111][112].…”

Section: Human Milk Oligosaccharidesmentioning

confidence: 99%

Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

et al. 2020

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Human breast milk is considered the optimum feeding regime for newborn infants due to its ability to provide complete nutrition and many bioactive health factors. Breast feeding is associated with improved infant health and immune development, less incidences of gastrointestinal disease and lower mortality rates than formula fed infants. As well as providing fundamental nutrients to the growing infant, breast milk is a source of commensal bacteria which further enhance infant health by preventing pathogen adhesion and promoting gut colonisation of beneficial microbes. While breast milk was initially considered a sterile fluid and microbes isolated were considered contaminants, it is now widely accepted that breast milk is home to its own unique microbiome. The origins of bacteria in breast milk have been subject to much debate, however, the possibility of an entero-mammary pathway allowing for transfer of microbes from maternal gut to the mammary gland is one potential pathway. Human milk derived strains can be regarded as potential probiotics; therefore, many studies have focused on isolating strains from milk for subsequent use in infant health and nutrition markets. This review aims to discuss mammary gland development in preparation for lactation as well as explore the microbial composition and origins of the human milk microbiota with a focus on probiotic development.

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Section: Human Milk Oligosaccharidesmentioning

confidence: 99%

Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

et al. 2020

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“…In the early stages of this program, we hypothesized that human milk oligosaccharides (HMOs) possess antimicrobial and antivirulence properties (25). Indeed, we discovered that heterogeneous HMOs modulate growth and biofilm production for a number of bacterial pathogens (26,27). We also determined the identities of several single-entity HMOs with potent antimicrobial activity against GBS (28)(29)(30)(31).…”

mentioning

confidence: 99%

A Solution to Antifolate Resistance in Group B Streptococcus : Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

Chambers

Moore

Craft

et al. 2020

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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.

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“…It contains lysozyme, an enzyme which destroys the structural peptidoglycan layer surrounding bacterial cells and which is recognized to be a key component of innate immunity (81). It also contains oligosaccharides which can inhibit bacterial growth and biofilm formation and sensitize them to antibiotics via membrane permeabilization (82)(83)(84)(85). Further, it contains the protein lactoferrin, which sequesters vital iron away from pathogenic bacteria.…”

Section: Results and Discussion Network Analysis Of Remedies For Skinmentioning

confidence: 99%

Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents

Connelly¹,

Genio

Harrison

2020

mBio

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The pharmacopeia used by physicians and laypeople in medieval Europe has largely been dismissed as placebo or superstition. While we now recognize that some of the materia medica used by medieval physicians could have had useful biological properties, research in this area is limited by the labor-intensive process of searching and interpreting historical medical texts. Here, we demonstrate the potential power of turning medieval medical texts into contextualized electronic databases amenable to exploration by the use of an algorithm. We used established methodologies from network science to reveal patterns in ingredient selection and usage in a key text, the 15th-century Lylye of Medicynes, focusing on remedies to treat symptoms of microbial infection. In providing a worked example of data-driven textual analysis, we demonstrate the potential of this approach to encourage interdisciplinary collaboration and to shine a new light on the ethnopharmacology of historical medical texts. IMPORTANCE We used established methodologies from network science to identify patterns in medicinal ingredient combinations in a key medieval text, the 15thcentury Lylye of Medicynes, focusing on recipes for topical treatments for symptoms of microbial infection. We conducted experiments screening the antimicrobial activity of selected ingredients. These experiments revealed interesting examples of ingredients that potentiated or interfered with each other's activity and that would be useful bases for future, more detailed experiments. Our results highlight (i) the potential to use methodologies from network science to analyze medieval data sets and detect patterns of ingredient combination, (ii) the potential of interdisciplinary collaboration to reveal different aspects of the ethnopharmacology of historical medical texts, and (iii) the potential development of novel therapeutics inspired by premodern remedies in a time of increased need for new antibiotics.

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Antimicrobial and Antibiofilm Activity of Human Milk Oligosaccharides against Streptococcus agalactiae, Staphylococcus aureus, and Acinetobacter baumannii

Cited by 82 publications

References 52 publications

Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

A Solution to Antifolate Resistance in Group B Streptococcus : Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents

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