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

Abstract

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_is of 2.47 μM and 73.38 μM, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a K_D of 44.65 μM for (-)-gallocatechin gallate and 16.45 μM for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 μg/mL for (-)-gallocatechin gallate and 250 μg/mL for rhodiosin against S. aureus. The current findings have the potential for identification of drugs to treat S. aureus infections by targeting SaSDH.

Keywords:

• Shikimate dehydrogenase
• Staphylococcus aureus
• virtual screening
• SaSDH inhibitors

Acknowledgements

The authors would like to express their gratitude to EditSprings (https://www.editsprings.cn) for the expert linguistic services provided.

Authors’ contributions

ZMF and DQ conceived and designed the experiments. ZMF and QJF prepared the materials and performed the experiments. ZMF, QJF and DQ analysed the computational data and results. The manuscript was organised and written by ZMF and DQ.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

The study was supported by Natural Science Foundation of Fujian Province [NO.2022J01672].