Targeted sortase A inhibition by novel peptidomimetic antivirulents against staphylococcal infections.

Antibiotic resistance is a critical public health issue, causing resistant bacterial strains to be increasingly difficult to control. Antivirulence therapies, which target bacterial virulence factors rather than kill bacteria, present a promising approach. Sortase enzymes, particularly SrtA, are crucial for gram-positive bacterial virulence by anchoring surface proteins essential for bacterial adhesion and biofilm formation to the bacterial outer cell wall. This study evaluates the selectivity of the peptidomimetic inhibitor BzLPRDSar toward various gram-positive bacteria. The BzLPRDSar significantly inhibited biofilm formation in multidrug-resistant IMPORTANCE: 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