Inhibition Mechanism of Mandelic Acid on the Activity of Sortase A of Staphylococcus aureus

Purpose To investigate the inhibitory effect of mandelic acid on the activity of Staphylococcus aureus sortase A (SrtA) and its molecular mechanism.

Method The in vitro inhibition effect of mandelic acid on S. aureus was studied by double dilution method and plate coating method; the growth curve of S. aureus in medium containing different concentrations of mandelic acid was determined; the determination of almonds by crystal violet staining method effects of mandelic acid on the formation of S. aureus biofilm; fluorescence resonance energy transfer assay (FRET), molecular docking technique and molecular dynamics were used to study the molecular mechanism of mandelic acid inhibititing the activity of S. aureus SrtA.

Result The MIC and MBC of mandelic acid against S. aureus were both greater than 1 024 μg/mL, and there was no effect on S. aureus and its growth within the test concentration range (0, 64, 128, 256, 512 and 1 024 μg/mL); the mass concentration of mandelic acid was different, and there was a slight difference in the total amount of S. aureus biofilm reduction and it was inhibited in a concentration-dependent manner; mandelic acid had a certain inhibitory effect on the SrtA activity, and its IC₅₀ was (66.15±24.39) μg/mL; mandelic acid is tightly bound to Pro-163, Val-166, Gly-167, Val-168, Ile-199 and Leu-169 residues by various intermolecular forces, resulting in conformational change of SrtA thereby reducing activity.

Conclusion Mandelic acid can bind tightly with the active center of SrtA and interact to form a stable complex, ultimately inhibiting the biological activity of SrtA, and has the potential to become an inhibitor against S. aureus infection.