Chaudhary Jyoti, Singh Nagendra, Srivastava Vijay Kumar, Jyoti Anupam, Kaushik Sanket
Keywords:
Enterococcus faecalis
, MDR bacteria, Diaminopimelate epimerase, Drug design
Enterococcus faecalis (E. faecalis) is a Gram-positive multidrug-resistant bacterium that is involved in almost 75% of all nosocomial infections. Most E. faecalis infections occur as a result of the use of E. faecalis harboring intravascular devices. The most common infections caused by E. faecalis are urinary tract infections, surgical site infections, and endocarditis. E. faecalis has a tendency to make biofilms on medical devices which makes it even more difficult to treat. Due to multidrug resistance nature of E. faecalis, it is now becoming essential to develop new compounds having antimicrobial activity. Therefore, it is necessary to target important proteins which are essential for the survival of E. faecalis and develop compounds that can bind and inhibit the activity of such proteins In E. faecalis, diaminopimelate epimerase (DapF) is an important enzyme involved in the metabolism of the amino acids lysine and mesoDap. Both of these metabolites are important as they have a significant role in several metabolic processes of bacteria such as peptidoglycan biosynthesis, synthesis of house-keeping proteins, and synthesis of other bacterial virulence factors. In a pathway involving the conversion of aspartate to lysine, DapF specifically catalyzes the isomerization of L, L- diaminopimelate to meso-DAP. This review provides a comprehensive overview of the structural and functional correlations of E. faecalis DapF. It provides a comparative structural analysis of DapF from E. faecalis and other pathogenic bacterial species. We have also emphasized on the existing approaches, paradoxes, and the prospects for the identification of potential inhibitors of E. faecalis DapF for treatment of E. faecalis infections.
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