Development of a small compound that regulates the function of a maltodextrin-binding protein of Streptococcus pyogenes by multifaceted screenings

Group A Streptococcus (GAS) are gram-positive bacteria that cause various symptoms. The treatment of GAS infections currently relies on antibiotics, but new treatment options are needed due to the spread of antibiotic resistance. To develop novel treatment methods that circumvent the generation of antibiotic resistance, we used virtual screening followed by several biophysical-based screening methods to identify antibacterial compounds that target SPs0871, which is a maltodextrin-binding protein that is involved in carbohydrate catabolism in GAS. We narrowed down the list of compounds in the library via multi-step screening and finally isolated a compound that bacteriostatically inhibited the growth of GAS. Together with our previous study showing that an anti-SPs0871 variable heavy domain of heavy chain antibody, which completely blocked ligand binding, did not suppress bacterial growth, our results provide guidelines for designing an antistreptococcal therapeutic.