The diverse antimicrobial activities of human milk oligosaccharides against Group B Streptococcus

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.

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Human Milk Oligosaccharides Reduce Murine Group B Streptococcus Vaginal Colonization with Minimal Impact on the Vaginal Microbiota

mSphere ◽

10.1128/msphere.00885-21 ◽

2022 ◽

Author(s):

Marlyd E. Mejia ◽

Samantha Ottinger ◽

Alison Vrbanac ◽

Priyanka Babu ◽

Jacob J. Zulk ◽

...

Keyword(s):

Preterm Birth ◽

Human Milk ◽

Group B Streptococcus ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Minimal Impact ◽

Vaginal Colonization ◽

Fetal Infection ◽

Serious Disease ◽

Group B

During pregnancy, GBS ascension into the uterus can cause fetal infection or preterm birth. In addition, GBS exposure during labor creates a risk of serious disease in the vulnerable newborn and mother postpartum.

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Murine monoclonal antibodies to type Ib polysaccharide of group B streptococci bind to human milk oligosaccharides.

Infection and Immunity ◽

10.1128/iai.60.4.1598-1602.1992 ◽

1992 ◽

Vol 60 (4) ◽

pp. 1598-1602 ◽

Cited By ~ 15

Author(s):

D G Pritchard ◽

B M Gray ◽

M L Egan

Keyword(s):

Monoclonal Antibodies ◽

Human Milk ◽

Human Milk Oligosaccharides ◽

Group B Streptococci ◽

Milk Oligosaccharides ◽

Group B ◽

Murine Monoclonal Antibodies

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Human milk oligosaccharides reduce murine group B Streptococcus vaginal colonization with minimal impact on the vaginal microbiota

10.1101/2021.10.20.465155 ◽

2021 ◽

Author(s):

Marlyd E Mejia ◽

Samantha Ottinger ◽

Alison Vrbanac ◽

Priyanka Babu ◽

Jacob Zulk ◽

...

Keyword(s):

Epithelial Cells ◽

Human Milk ◽

Biofilm Formation ◽

Group B Streptococcus ◽

Human Milk Oligosaccharides ◽

Vaginal Colonization ◽

Vaginal Epithelial Cells ◽

Group B

Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. Recently, human milk oligosaccharides (HMOs) isolated from breastmilk were found to inhibit GBS growth and biofilm formation in vitro, and women that make certain HMOs are less likely to be vaginally colonized with GBS. Using in vitro human vaginal epithelial cells and a murine vaginal colonization model, we tested the impact of HMO treatment on GBS burdens and the composition of the endogenous microbiota by 16S rRNA amplicon sequencing. HMO treatment reduced GBS vaginal burdens in vivo with minimal alterations to the vaginal microbiota. HMOs displayed potent inhibitory activity against GBS in vitro, but HMO pretreatment did not alter adherence of GBS or the probiotic Lactobacillus rhamnosus to human vaginal epithelial cells. Additionally, disruption of a putative GBS glycosyltransferase (Δsan_0913) rendered the bacterium largely resistant to HMO inhibition in vitro and in vivo but did not compromise its adherence, colonization, or biofilm formation in the absence of HMOs. We conclude that HMOs are a promising therapeutic bioactive to limit GBS vaginal colonization with minimal impacts on the vaginal microenvironment.

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Human Milk Oligosaccharides Exhibit Biofilm Eradication Activity Against Matured Biofilms Formed by Different Pathogen Species

Frontiers in Microbiology ◽

10.3389/fmicb.2021.794441 ◽

2022 ◽

Vol 12 ◽

Author(s):

Sylwia Jarzynka ◽

Riccardo Spott ◽

Tinatini Tchatchiashvili ◽

Nico Ueberschaar ◽

Mark Grevsen Martinet ◽

...

Keyword(s):

Human Milk ◽

Pathogenic Bacteria ◽

Biological Significance ◽

Burkholderia Cenocepacia ◽

Respiratory Pathogens ◽

Human Milk Oligosaccharides ◽

Group B Streptococci ◽

Milk Oligosaccharides ◽

Gram Positive ◽

Group B

Human milk oligosaccharides (HMOs) have been shown to exhibit plenty of benefits for infants, such as prebiotic activity shaping the gut microbiota and immunomodulatory and anti-inflammatory activity. For some pathogenic bacteria, antimicrobial activity has been proved, but most studies focus on group B streptococci. In the present study, we investigated the antimicrobial and antibiofilm activities of the total and fractionated HMOs from pooled human milk against four common human pathogenic Gram-negative species (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cenocepacia) and three Gram-positive species (Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis). The activity of HMOs against enterococci and B. cenocepacia are addressed here for the first time. We showed that HMOs exhibit a predominant activity against the Gram-positive species, with E. faecalis being the most sensitive to the HMOs, both in planktonic bacteria and in biofilms. In further tests, we could exclude fucosyllactose as the antibacterial component. The biological significance of these findings may lie in the prevention of skin infections of the mother’s breast as a consequence of breastfeeding-induced skin laceration and/or protection of the infants’ nasopharynx and lung from respiratory pathogens such as staphylococci.

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