Interrogation of Human Milk Oligosaccharide Fucosylation Patterns for Antimicrobial and Antibiofilm Trends in Group B Streptococcus

For newborns, human milk oligosaccharides (HMOs) serve as an important source of protection against bacterial pathogens. HMOs prevent infection by functioning as decoy receptors that bind pathogens to inhibit cellular adhesion. HMOs also play a protective role by acting as prebiotics that selectively promote the growth of symbiotic gut bacteria over pathogens. Fucosylated HMOs in particular are well-known for their roles as both decoy receptors and prebiotics. Recently, we discovered that HMOs possess antimicrobial activity against Group B Streptococcus (GBS) by increasing cellular permeability. HMO extracts from a single donor can contain over 100 different structures; however, studies using heterogeneous HMO mixtures do not provide insight into the specific structural requirements needed to achieve antimicrobial activity. In this study, we address this void by completing a structure activity study on the antimicrobial and antibiofilm activities of six neutral, fucosylated and five neutral, nonfucosylated HMOs against GBS. We determined that while the presence of fucose alone does not correlate to antimicrobial activity, the location and degree of fucosylation does play a key role in the antimicrobial activity of HMOs. Moreover, the antimicrobial and antibiofilm activities of single HMOs were found to be strain-specific. This further supports our vision of developing narrow-spectrum antibacterial agents against GBS.