Superbug Neisseria gonorrhoeae Infections: The Role of the Moonlighting Protein Glutamate Racemase in Treatment and Prevention.

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Neisseria gonorrhoeae is a notorious superbug responsible for causing 'Gonorrhoea' in humans. Recently, it has been classified as a high-priority pathogen by the World Health Organization due to its increasing resistance to available antibiotics. A multi-prolonged approach is needed to combat the growing problem of drug resistance caused by N. gonorrhoeae. This study evaluates Glutamate Racemase (GR), a moonlighting protein of N. gonorrhoeae (Ng- GR), as a novel therapeutic target with potential for both inhibitor design and peptide vaccine development. Ng-GR plays a crucial role in the peptidoglycan biosynthetic pathway and is highly conserved across bacterial species. Additionally, this protein moonlights to perform a secondary function by binding to DNA gyrase in various organisms. Homology modeling, molecular docking, and molecular dynamics simulations were used to design inhibitors targeting the moonlight function of Ng-GR. The immunogenicity of this protein was assessed using ABCPred-2.0, BepiPred-2.0, and ProPred software. Bisleucocurine A was found to bind at the ectopic site of Ng-GR, disrupting its crucial moonlight function and interfering with the interaction between Ng-GR and N. gonorroheae DNA Gyrase (Ng-gyrase). Interestingly, residues important for its moonlight function were also identified as key immunogenic sites using ABCPred-2.0, BepiPred-2.0, and ProPred software, enhancing the potential of this protein as a vaccine candidate. The GR enzyme's moonlight function is highlighted as a promising novel target for therapeutic intervention and vaccine development in N. gonorrohoeae.