Identification of potential inhibitors against Staphylococcus aureus shikimate dehydrogenase through virtual screening and susceptibility test

Staphylococcus aureus shikimate dehydrogenase (SaSDH) plays a crucial role in the growth of Staphylococcus aureus (S. aureus), but absent in mammals and therefore a potential target for antibacterial drugs to treat drug-resistant S. aureus infection. In this study, a 3D model of SaSDH was constructed by homology modelling and inhibitors of SaSDH were screened through virtual screening. (-)-Gallocatechin gallate and rhodiosin were identified as inhibitors with K(i)s of 2.47 mu M and 73.38 mu M, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a K-D of 44.65 mu M for (-)-gallocatechin gallate and 16.45 mu M for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 mu g/mL for (-)-gallocatechin gallate and 250 mu g/mL for rhodiosin against S. aureus. The current findings have the potential for identification of drugs to treat S. aureus infections by targeting SaSDH.