biostudies-literatureHayashida ANEI NIH HHSe9https://www.ebi.ac.uk/biostudies/studies/S-EPMC11218895biostudies-literatureUnknown1(3)A large number of bacterial pathogens bind to host extracellular matrix (ECM) components. For example, many Gram-negative and Gram-positive pathogens express binding proteins for fibronectin (FN) on their cell surface. Mutagenesis studies of bacterial FN-binding proteins have demonstrated their importance in pathogenesis in preclinical animal models. However, means to draw on these findings to design therapeutic approaches that specifically target FN-bacteria interactions have not been successful because bacterial pathogens can elaborate several FN-binding proteins and also because FN is an essential protein and likely a nondruggable target. Here we report that select heparan compounds potently inhibit <i>Streptococcus pneumoniae</i> infection of injured corneas in mice. Using intact heparProteoglycan researchSulfated motifs in heparan sulfate inhibit <i>Streptococcus pneumoniae</i> adhesion onto fibronectin and attenuate corneal infection.PMC11218895R01 EY021765R01 EY033025Zhang FLiu JSaeed HNParks WCBispo PJMHayashida APark PWSong YfalseSulfated motifs in heparan sulfate inhibit <i>Streptococcus pneumoniae</i> adhesion onto fibronectin and attenuate corneal infection.A large number of bacterial pathogens bind to host extracellular matrix (ECM) components. For example, many Gram-negative and Gram-positive pathogens express binding proteins for fibronectin (FN) on their cell surface. Mutagenesis studies of bacterial FN-binding proteins have demonstrated their importance in pathogenesis in preclinical animal models. However, means to draw on these findings to design therapeutic approaches that specifically target FN-bacteria interactions have not been successful because bacterial pathogens can elaborate several FN-binding proteins and also because FN is an essential protein and likely a nondruggable target. Here we report that select heparan compounds potently inhibit <i>Streptococcus pneumoniae</i> infection of injured corneas in mice. Using intact hepar2023-01-01T00:00:00Z2023 Jul2025-04-04T23:54:14.714Z2025-04-04T23:54:14.714ZS-EPMC112188953895762210.1002/pgr2.9