Targeted sortase A inhibition by novel peptidomimetic antivirulents against staphylococcal infections

Antibiotic resistance is making it harder to treat bacterial infections, even with our strongest medicines. This study explores a new approach that does not aim to kill bacteria but instead disarms them by blocking the tools they use to cause disease. We focused on a bacterial enzyme called sortase A (SrtA), which helps harmful bacteria stick to surfaces and form protective layers called biofilms-structures that make infections very difficult to treat. We tested a specially designed molecule, BzLPRDSar, and found it could stop biofilm formation in drug-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. It was less effective against other bacteria, likely because of differences in the SrtA enzyme sequences. Our findings suggest that targeting virulence rather than killing bacteria may offer a safer and more sustainable way to treat infections, especially those caused by bacteria that no longer respond to antibiotics.