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 <i>Staphylococcus aureus</i> and <i>Staphylococcus epidermidis</i>. 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.