Streptococcus pneumoniae capsular polysaccharide is linked to peptidoglycan via a direct glycosidic bond to β-D- N -acetylglucosamine

Significance Bacterial surface polysaccharides form the interface between the bacterium and its environment. In Gram-positive bacteria, the intricate architecture of the peptidoglycan (PG) serves as the scaffolding to which other surface polysaccharides, including capsules, can be anchored. For pathogenic bacteria, proper localization of capsular polysaccharide (CPS) is essential to cause disease. In Streptococcus pneumoniae , CPS is also the primary target for vaccines. Here, we identify a structure for polysaccharide attachment to PG that involves a direct glycosidic linkage. Knowledge of this linkage lays the groundwork for identifying the enzyme(s) involved in its synthesis and for developing new targets for therapeutic interventions.