Screening and Identification of Natural Compounds as Potential Inhibitors of Glutamate Racemase, an Emerging Drug Target of Food Pathogen O157:H7: An Approach to Combat Increasing Drug Resistance.

BACKGROUND

Shiga Toxin-Producing Escherichia coli () O157:H7, capable of causing serious food-borne illnesses, is extensively studied and is known to be transmitted through animal reservoirs or person-to-person contact, leading to severe disease outbreaks. The emergence of antibiotic resistance in these strains, coupled with increased adverse effects of existing therapeutics, underscores the urgent need for alternative therapeutic strategies.

OBJECTIVE

This study aims to evaluate Glutamate Racemase (MurI protein) of the food-pathogenic O157:H7 (EC MurI) as a novel drug target. Furthermore, the study seeks to identify new compounds with potential inhibitory effects against this protein.

METHODS

Using computational tools, the study identified inhibitor binding sites on EC MurI and identified relevant inhibitors capable of binding to these sites. Molecular docking techniques were employed to assess potential hits, and selected compounds were further analyzed for their structural activity and binding affinity to the protein.

RESULTS

The results of the study revealed that Frigocyclinone and Deslanoside, exhibited the best binding affinity with EC-MurI. Subsequent molecular dynamic (MD) simulations of the selected complexes indicated that both compounds were stable. This suggests that Frigocyclinone and Deslanoside have the potential to serve as potent inhibitors of EC-MurI.

CONCLUSION

In summary, this study highlights the urgent need for alternative therapies against food-pathogenic , focusing on O157:H7. Evaluation of Glutamate Racemase as a drug target identified Frigocyclinone and Deslanoside as promising inhibitors. MD simulations indicated their stability, suggesting their potential as lead molecules for further research and treatment development.