Human milk oligosaccharides inhibit growth of group B Streptococcus

J Biol Chem. 2017 Jul 7;292(27):11243-11249. doi: 10.1074/jbc.M117.789974. Epub 2017 Apr 17.


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.

Keywords: Streptococcus; antimicrobial; bacteria; glycobiology; glycosyltransferase; human milk oligosaccharide; infectious disease; lacto-N-tetraose; oligosaccharide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Female
  • Humans
  • Milk, Human / chemistry*
  • Oligosaccharides / chemistry
  • Oligosaccharides / isolation & purification
  • Oligosaccharides / pharmacology*
  • Streptococcus agalactiae / genetics
  • Streptococcus agalactiae / growth & development*


  • Anti-Bacterial Agents
  • Oligosaccharides