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Human milk oligosaccharides inhibit growth of group B Streptococcus
Ann E Lin1, Chloe A Autran2,3, Alexandra Szyszka2,3
1From the Divisions of Host-Microbe Systems and Therapeutics.
Insights
Human milk oligosaccharides (HMOs) directly inhibit the growth of group B Streptococcus (GBS), a major neonatal pathogen. This novel antibacterial property, independent of host immunity, offers new therapeutic potential.
Area of Science:
- Microbiology
- Immunology
- Neonatal Health
Background:
- Group B Streptococcus (GBS) causes severe infections in newborns via maternal transmission.
- Human milk oligosaccharides (HMOs) are crucial for infant immunity and gut microbiota development.
- HMOs are known to protect against pathogen colonization.
Purpose of the Study:
- To investigate the direct impact of HMOs on GBS growth.
- To identify specific HMOs with antibacterial activity against GBS.
- To explore the mechanism of HMO-GBS interaction.
Main Methods:
- Fractionation of HMOs using multidimensional chromatography.
- Testing HMO fractions for bacteriostatic activity against GBS.
- Phenotypic screening of a GBS transposon insertion library.
- Identifying GBS genes involved in HMO resistance.
Main Results:
- Specific non-sialylated HMOs demonstrated direct bacteriostatic effects on GBS.
- HMO activity was synergistic with conventional antibiotics.
- A GBS-specific gene encoding a putative glycosyltransferase was identified as conferring HMO resistance.
Conclusions:
- HMOs possess a previously unrecognized direct antibacterial role against the neonatal pathogen GBS.
- This activity is mediated by specific HMO structures and involves a GBS glycosyltransferase.
- HMOs represent a promising therapeutic strategy for combating GBS infections in neonates.
Abstract:
Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of invasive bacterial infections in newborns, typically acquired vertically during childbirth secondary to maternal vaginal colonization. Human milk oligosaccharides (HMOs) have important nutritional and biological activities that guide the development of the immune system of the infant and shape the composition of normal gut microbiota. In this manner, HMOs help protect against pathogen colonization and reduce the risk of infection. In the course of our studies of HMO-microbial interactions, we unexpectedly uncovered a novel HMO property to directly inhibit the growth of GBS independent of host immunity. By separating different HMO fractions through multidimensional chromatography, we found the bacteriostatic activity to be confined to specific non-sialylated HMOs and synergistic with a number of conventional antibiotic agents. Phenotypic screening of a GBS transposon insertion library identified a mutation within a GBS-specific gene encoding a putative glycosyltransferase that confers resistance to HMOs, suggesting that HMOs may function as an alternative substrate to modify a GBS component in a manner that impairs growth kinetics. Our study uncovers a unique antibacterial role for HMOs against a leading neonatal pathogen and expands the potential therapeutic utility of these versatile molecules.