Metabolization of human milk oligosaccharides by Streptococcus pneumoniae

Abstract It is unclear whether human milk oligosaccharides (HMOs) can be used as a nutrient source by Streptococcus pneumoniae . Here, we investigate whether and how S. pneumoniae metabolizes HMOs and whether these compounds inhibit pneumococcal adherence. We find that S. pneumoniae can metabolize several HMOs, except for 2’-fucosyllactose (2’FL). The process is regulated by the carbon catabolite repression system. Transcriptome analyses showed reduced expression of the lac operon I ( lacABCD ) in bacteria grown with two tested HMOs when compared to lactose (Lac). Genes for the Leloir pathway and exoglycosidases were upregulated. A genome-wide CRISPR interference screen showed that the lac operons I and II ( lacEFG-2 ) are essential for metabolizing HMOs. Lac and non-metabolizable 2’FL were found to inhibit pneumococcal adherence to host cells in vitro. Importantly, 2’FL showed a stronger inhibitory effect compared to Lac in vivo. Further research is warranted to investigate whether the non-metabolizable 2’FL can be used to inhibit pneumococcal adherence.