Background Neisseria gonorrhoeae (NG) is a sexually transmitted pathogen infecting both men and women. In spite of a number of antibiotics, gonorrhea (also known as “The Clap”), remains a frequently reported STI and is an important cause of pelvic inflammatory disease and infertility. Due to resistance to most of the currently used drugs, NG has been named as ‘Superbug’ posing a serious threat to gonorrhoea treatment worldwide. Therefore, there is an urgent need to find novel drug targets and to develop new antibacterial agents.

Methods Using system biology to identify potential drug targets and the known inhibitors/drugs against homologous proteins, we identified a novel drug target, namely glutamate racemase (GR). This enzyme is involved in the early phase of peptidoglycan biosynthesis in both gram positive and gram negative bacteria. As protein-ligand interactions play a key role in structure-based drug design, we screened natural compounds for binding to NG-GR by carrying out docking studies, shortlisted the best docked compounds and evaluated them for their functional, structural and antibacterial activity.

Results The computational analysis showed that the coumarin derivative-esculetin exhibited best binding affinity among all the tested compounds. Characterization of the biophysical properties of purified recombinant GR using circular dichroism, in the absence and presence of esculetin, indicated a change in protein conformation in the presence of esculetin. This change is the protein structure was associated with a concomitant inhibition of racemization activity of recombinant GR. Esculetin also inhibited the growth of the bacteria in culture both in time and concentration dependent manner.

Conclusion In conclusion, these observations could provide impetus for further research in this direction. Better understanding of antibacterial mechanisms of esculetin will help in establishing lead molecules for the treatment of gonococcal infections.

Disclosure No significant relationships.