a non-beta-lactam antibiotic inhibitor for enterohemorrhagic escherichia coli o104:h4

The overuse of antibiotics has caused an increased prevalence of drug-resistant bacteria. bacterial resistance in e. coli is regulated via production of β-lactam-hydrolyzing β-lactamases enzymes. escherichia coli o104: h4 is a multi-drug resistant strain known to resist β-lactam as well as several other antibiotics. here, we report a molecular dynamic simulation–combined docking approach to identify, screen, and verify active pharmacophores against enterohemorrhagic escherichia coli (ehec). experimental studies revealed a boronic acid cyclic monomer (bacm), a non-β-lactam compound, to inhibit the growth of e. coli o104: h4. in vitro kirby bauer disk diffusion susceptibility testing coupled interaction analysis suggests bacm inhibits e. coli o104:h4 growth by not only inhibiting the β-lactamase pathway but also via direct inhibition of the penicillin-binding protein. these results suggest that bacm could be used as a lead compound to develop potent drugs targeting beta-lactam resistant gram-negative bacterial strains. • an in silico approach was reported to identify pharmacophores against e. coli o104: h4. • in vitro studies revealed a non-β-lactam compound to inhibit the growth of e. coli o104: h4. • this non-β-lactam compound could be used as a lead compound for targeting beta-lactam strains.