**4. Conclusion**

Increasing concerns associated with overusing antibiotics in animals and humans make it urgent to find new alternatives for treating bacterial infections and diseases. BCAA pathways enzymes are promising antimicrobial alternatives being developed as potential drug targets absent in animals and humans. Comparative studies of KARI from different bacteria bestows the idea that this essential enzyme can be targeted for anti-bacterial drug design. Therefore, KARI is considered a good target, due to a non-homologous protein in comparison with human proteins, and its targeting will be safe for humans. In this review, we assess the presence of KARI in most human pathogens, especially the ESKAPE group, due to its high antibiotic-resistance causing severe infections.

Since the 3D structure for KARI from *N. gonorrhoeae* was nonreported yet, a model of this enzyme was produced using the Swiss model. Indeed, the *Ng* KARI was modeled in silico based on X-ray crystallography structure for *Sa* KARI, used as a template. It was evaluated that cofactors ligands (Mg2+ and NADPH) were conserved among human bacterial pathogens. Upon the binding of these cofactors, KARI adapts a different conformation allowing the substrate binding and catalysis, while the active site adapt to a closed state.

Competitive inhibitors, targeting the active site are promoting drugs for the growth inhibition of pathogens. However, the NADPH binding site and the active site are highly conserved among bacteria, including the gut microbiome. In fact, a growing number of studies have shown that antibiotics can result in microbial dysbiosis, due to their broad-spectrum activities, when subsets of commensal
