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

2022 ◽  
Vol 12 ◽  
Author(s):  
Sylwia Jarzynka ◽  
Riccardo Spott ◽  
Tinatini Tchatchiashvili ◽  
Nico Ueberschaar ◽  
Mark Grevsen Martinet ◽  
...  

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.

2020 ◽  
Author(s):  
Sylwia Jarzynka ◽  
Kamila Strom ◽  
Oliwia Makarewicz ◽  
Anna Minkiewicz-Zochniak ◽  
Anna Koryszewska-Baginska ◽  
...  

<p><strong>Background</strong>: Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk, after fat and lactose, that promote infant health. Recent studies have shown that HMOs demonstrated antimicrobial and antibiofilm activity against different strains. Cystic fibrosis (CF), it is one of the major respiratory diseases, the clinical management and definitive treatment of CF biofilm-mediated chronic bacterial lung infection remains a challenge.</p> <p><strong>Objective</strong>: In this study, we examine HMOs antibiofilm activity against pathogens isolated from CF patients.</p> <p><strong>Methods and results</strong>: In current work, we investigated the antibiofilm activity of the saccharide fraction obtained from pooled human milk of 9 donors against strains of: <em>Acinetobacter baumannii</em>, <em>Pseudomonas aeruginosa</em>, <em>Enterobacteriaceae</em>, <em>Staphylococcus aureus</em> and <em>Burkholderia cenocepacia</em>, an intrinsically multi-resistant pathogen associated with high mortality in CF patients. We tested the ability of HMOs to inhibit biofilm formation and to eradicate matured biofilms. Live/dead staining of the biofilms and CLSM image acquisition were used.</p> <p>The pooled HMOs showed a biofilm eradicating effect on most tested pathogens. The HMOs effectively killed the bacteria at high concentration (20 mg/ml, corresponds to the concentration in human milk), but visible reduction of viable bacteria and biofilm mass was observed already at lower concentrations that varied between the species. The biofilm mass was also reduced in almost all pathogenic biofilms.</p> <p>The data presented in this paper supporting the importance and potential inhibitory effect of HMOs in biofilm formation. HMOs could potentially be used as novel therapeutics to treat or prevent infectious disease in patient with CF.</p>


2007 ◽  
Vol 79 (12) ◽  
pp. 2229-2242 ◽  
Author(s):  
El Sayed H. El Ashry ◽  
Mohamed R. E. Aly

The structural diversity as well as the biological significance of N-acetylglucosamine-containing glycans are exemplified. The problem of forming the respective glycosidic bonds of synthetic targets is addressed. Special emphasis has been given to human milk oligosaccharides (HMOs), in view of their biological relevance, and synthetic approaches of selected examples are reported.


2017 ◽  
Vol 8 (2) ◽  
pp. 281-289 ◽  
Author(s):  
S. Musilova ◽  
N. Modrackova ◽  
P. Hermanova ◽  
T. Hudcovic ◽  
R. Svejstil ◽  
...  

The mode of delivery plays a crucial role in infant gastrointestinal tract colonisation, which in the case of caesarean section is characterised by the presence of clostridia and low bifidobacterial counts. Gut colonisation can be modified by probiotics, prebiotics or synbiotics. Human milk oligosaccharides (HMOs) are infant prebiotics that show a bifidogenic effect. Moreover, genome sequencing of Bifidobacterium longum subsp. infantis within the infant microbiome revealed adaptations for milk utilisation. This study aimed to evaluate the synbiotic effect of B. longum subsp. infantis, HMOs and human milk (HM) both in vitro and in vivo (in a humanised mouse model) in the presence of faecal microbiota from infants born by caesarean section. The combination of B. longum and HMOs or HM reduced the clostridia and G-bacteria counts both in vitro and in vivo. The bifidobacterial population in vitro significantly increased and produce high concentrations of acetate and lactate. In vitro competition assays confirmed that the tested bifidobacterial strain is a potential probiotic for infants and, together with HMOs or HM, acts as a synbiotic. It is also able to inhibit potentially pathogenic bacteria. The synbiotic effects identified in vitro were not observed in vivo. However, there was a significant reduction in clostridia counts in both experimental animal groups (HMOs + B. longum and HM + B. longum), and a specific immune response via increased interleukin (IL)-10 and IL-6 production. Animal models do not perfectly mimic human conditions; however, they are essential for testing the safety of functional foods.


2016 ◽  
Vol 5 (8) ◽  
pp. e99 ◽  
Author(s):  
Nicholas J Andreas ◽  
Asmaa Al-Khalidi ◽  
Mustapha Jaiteh ◽  
Edward Clarke ◽  
Matthew J Hyde ◽  
...  

2005 ◽  
Vol 389 (2) ◽  
pp. 325-332 ◽  
Author(s):  
Stéphanie Perret ◽  
Charles Sabin ◽  
Claire Dumon ◽  
Martina Pokorná ◽  
Catherine Gautier ◽  
...  

One of the mechanisms contributing to the protection by breast-feeding of the newborn against enteric diseases is related to the ability of human milk oligosaccharides to prevent the attachment of pathogenic bacteria to the duodenual epithelium. Indeed, a variety of fucosylated oligosaccharides, specific to human milk, form part of the innate immune system. In the present study, we demonstrate the specific blocking of PA-IIL, a fucose-binding lectin of the human pathogen Pseudomonas aeruginosa, by milk oligosaccharides. Two fucosylated epitopes, Lewis a and 3-fucosyl-lactose (Lewis x glucose analogue) bind to the lectin with dissociation constants of 2.2×10−7 M and 3.6×10−7 M respectively. Thermodynamic studies indicate that these interactions are dominated by enthalpy. The entropy contribution is slightly favourable when binding to fucose and to the highest-affinity ligand, Lewis a. The high-resolution X-ray structures of two complexes of PA-IIL with milk oligosaccharides allow the precise determination of the conformation of a trisaccharide and a pentasaccharide. The different types of interaction between the oligosaccharides and the protein involve not only hydrogen bonding, but also calcium- and water-bridged contacts, allowing a rationalization of the thermodynamic data. This study provides important structural information about compounds that could be of general application in new therapeutic strategies against bacterial infections.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Schuyler A. Chambers ◽  
Rebecca E. Moore ◽  
Kelly M. Craft ◽  
Harrison C. Thomas ◽  
Rishub Das ◽  
...  

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.


mSphere ◽  
2022 ◽  
Author(s):  
Marlyd E. Mejia ◽  
Samantha Ottinger ◽  
Alison Vrbanac ◽  
Priyanka Babu ◽  
Jacob J. Zulk ◽  
...  

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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