A non-beta-lactam antibiotic inhibitor for enterohemorrhagic Escherichia coli O104:H4

AbstractThe overuse of antibiotics has caused an increased prevalence of drug-resistant bacteria. Bacterial resistance inE. 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 enterohemorrhagicEscherichia coli (EHEC). Experimental studies revealed a boronic acid cyclic monomer (BACM), a non- β-lactam compound, to inhibit the growth ofE. coli O104: H4. In vitro Kirby Bauer disk diffusion susceptibility testing coupled interaction analysis suggests BACM inhibitsE. 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.Key messages• An in silico approach was reported to identify pharmacophores againstE. coli O104: H4.• In vitro studies revealed a non-β-lactam compound to inhibit the growth ofE. coli O104: H4.• This non-β-lactam compound could be used as a lead compound for targeting beta-lactam strains.
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research