Unique Diacidic Fragments Inhibit the OXA-48 Carbapenemase and Enhance the Killing of Escherichia coli Producing OXA-48.

ABSTRACT: Despite the advances in β-lactamase inhibitor development, limited options exist for the class D carbapenemase known as OXA-48. OXA-48 is one of the most prevalent carbapenemases in carbapenem-resistant Enterobacteriaceae infections and is not susceptible to most available β-lactamase inhibitors. Here, we screened various low-molecular-weight compounds (fragments) against OXA-48 to identify functional scaffolds for inhibitor development. Several biphenyl-, naphthalene-, fluorene-, anthraquinone-, and azobenzene-based compounds were found to inhibit OXA-48 with low micromolar potency despite their small size. Co-crystal structures of OXA-48 with several of these compounds revealed key interactions with the carboxylate-binding pocket, Arg214, and various hydrophobic residues of β-lact

SUBMITTER: Taylor DM 

PROVIDER: S-EPMC9677231 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature