A non-beta-lactam antibiotic inhibitor for enterohemorrhagic Escherichia coli O104:H4.
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abstract
The overuse of antibiotics has caused an increased prevalence of drug-resistant bacteria. Bacterial resistance in E. coli is regulated via production of -lactam-hydrolyzing -lactamases enzymes. Escherichia coli O104: H4 is a multi-drug resistant strain known to resist -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--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 -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. KEY MESSAGES: An in silico approach was reported to identify pharmacophores against E. coli O104: H4. In vitro studies revealed a non--lactam compound to inhibit the growth of E. coli O104: H4. This non--lactam compound could be used as a lead compound for targeting beta-lactam strains.
