Human Milk Oligosaccharides as a Defense Against Group B Streptococcus

Abstract

Streptococcus agalactiae (Group B strep, GBS) is a common infant pathogen that causes sepsis and meningitis. Human milk provides nutrition for the developing infant, and breast milk consumption leads to critical modulation of the host immune development, which promotes both tolerance and immunity. This protection is due, in part, to human milk oligosaccharides (HMOs). Minimal research has been done to study the interaction between human milk and GBS. In this work, we describe the ability of HMOs isolated from donor milk to modulate both the proliferation and biofilm production of GBS and affirm the importance of HMOs in infant health. To further probe the individual oligosaccharides responsible for the antimicrobial and anti-biofilm properties of HMOs, we developed a succinct and scalable synthesis of several human milk trisaccharides and unnatural congeners. The synthesis and direct glycosylation of a lactose acceptor with several donors furnished compounds that are or resemble small HMOs. Biological evaluation of these compounds against GBS revealed the antimicrobial and anti-biofilm properties are likely associated with terminally fucosylated and galactosylated species.