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.
Highlights
Streptococcus agalactiae is a leading cause of invasive bacterial infections in newborns, typically acquired vertically during childbirth secondary to maternal vaginal colonization
We demonstrated that Human milk oligosaccharides (HMOs) regulate the host innate immune response in bladder epithelial cells to prevent invasion and cytotoxicity caused by uropathogenic Escherichia coli (UPEC) without any direct interference with bacterial growth [20]
To evaluate the potential antimicrobial effect(s) of HMO on a group of bacterial pathogens, we resuspended ϳ105 cfu of each bacterial overnight culture in serum-free tissue culture medium (RPMI) with or without 2 mg/ml of HMOs isolated from pooled human milk and incubated for 4 h. pHMOs did not affect the growth of UPEC, P. aeruginosa, and methicillin-resistant S. aureus
Summary
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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. HMOs are not digested by the infant and reach the colon intact, where they serve as metabolic substrates for specific, potentially beneficial bacteria and help shape the infant microbiome. HMOs are partially absorbed and reach the systemic circulation of the tral human milk oligosaccharide; LNT, lacto-N-tetraose; LNnT, lacto-Nneotetraose; LNnH, lacto-N-neohexaose; LNFPI, lacto-N-fucopentaose I; LNDFHII, lacto-N-difucohexaose II; LnNO, lacto-N-neooctaose; LNnDFH, lacto-N-neodifucohexaose; LNnFPV, lacto-N-neofucopentaose; LNFPV, lacto-N-fucopentaose V; THB, Todd-Hewitt broth; SF-RPMI 1640, serumfree RPMI 1640; ANOVA, analysis of variance
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