Identification of Peptidoglycan Glycosyltransferase FtsI as a Potential Drug Target against and Serovars Through Subtractive Genomics, Molecular Docking and Molecular Dynamics Simulation Approaches.

INTRODUCTION

serovar Enteritidis and serovar Typhimurium are among the main causative agents of nontyphoidal Salmonella infections, imposing a significant global health burden. The emergence of antibiotic resistance in these pathogens underscores the need for innovative therapeutic strategies.

OBJECTIVE

To identify proteins as potential drug targets against and Salmonella Typhimurium serovars using approaches.

METHODS

In this study, a subtractive genomics approach was employed to identify potential drug targets. The whole proteome of PT4 and (D23580), containing 393 and 478 proteins, respectively, was analyzed through subtractive genomics to identify human homologous proteins of the pathogen and also the proteins linked to shared metabolic pathways of pathogen and its host.

RESULTS

Subsequent analysis revealed 19 common essential proteins shared by both strains. To ensure hostspecificity, we identified 10 non-homologous proteins absent in humans. Among these proteins, peptidoglycan glycosyltransferase FtsI was pivotal, participating in pathogen-specific pathways and making it a promising drug target. Molecular docking highlighted two potential compounds, Balsamenonon A and 3,3',4',7-Tetrahydroxyflavylium, with strong binding affinities with FtsI. A 100 ns molecular dynamics simulation having 10,000 frames substantiated the strong binding affinity and demonstrated the enduring stability of the predicted compounds at the docked site.

CONCLUSION

The findings in this study provide the foundation for drug development strategies against Salmonella infections, which can contribute to the prospective development of natural and cost-effective drugs targeting and .