Abstract:
The rise of multidrug-resistant Escherichia coli O157:H7 poses a significant threat to public
health, necessitating the identification of novel therapeutic targets and alternative treatment
strategies. The bacterium’s ability to survive under various stress conditions poses a significant
challenge in developing effective therapeutic strategies. This study employed a systems biology
approach to identify stress-responsive genes as potential drug targets. Differential gene
expression analysis revealed 7 commonly upregulated genes (mnmG, yeiR, rnhB, rsxB, rsxC,
emrA, lpxP) under chemical preservative, natural antimicrobial, and acid stress conditions.
Homology analysis highlighted EmrA, LpxP, RsxB, and RsxC as bacterial specific proteins.
Protein-protein interaction and functional enrichment analysis highlighted these proteins as key
survival-associated proteins of E. coli O157:H7.
Structural characterization and molecular docking studies identified Telmisartan,
Cyclobenzaprine HCl, Loperamide HCl and Irinotecan as promising repurposed drugs with
strong binding affinities of -9.2, -8.8, -8, and -8.6 respectively to the bacterial targets.
Experimental validation using MIC and MBC assays confirmed the antibacterial efficacy of
Telmisartan and Cyclobenzaprine showing bacteriostatic effects at 62.5 μg/ml and bactericidal
effects at 250 μg/ml for both drugs. These findings suggest that repurposed drugs targeting
EmrA, LpxP, RsxB, and RsxC, could be promising candidates against E. coli O157:H7. Future
research should focus on optimizing drug formulations and in-vivo validations to enhance
therapeutic potential.
