Human milk oligosaccharides inhibit growth of group B Streptococcus

Ann E. Lin, Chloe A. Autran, Alexandra Szyszka, Tamara Escajadillo, Mia Huang, Kamil Godula, Anthony R. Prudden, Geert Jan Boons, Amanda L. Lewis, Kelly S. Doran, Victor Nizet, Lars Bode

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

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. Pheno-typic 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.

Original languageEnglish
Pages (from-to)11243-11249
Number of pages7
JournalJournal of Biological Chemistry
Volume292
Issue number27
DOIs
StatePublished - Jul 7 2017

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