Previous in vivo studies have suggested that S. pneumoniae binds to FN fibrils in the basement membrane when infecting injured corneas.12 Furthermore, the FN binding site in HS is resistant to heparinase III digestion, whereas it is susceptible to heparinase I digestion.49 Together with our data showing that HS inhibition of S. pneumoniae corneal infection is sensitive to heparinase I, but not to heparinase III digestion, these findings suggest that HS and HP are inhibiting infection by interfering with S. pneumoniae interactions with FN. Here, FN1 is linked to infection.