There may be a way for some NSAIDs to play a role in disrupting bacterial DNA and replication, and contributing to the fight against antibiotic resistance, according to a report.
Lab work has shown antibacterial properties of carprofen, bromfenac and vedaprofen, which inhibit the Escherichia coli DNA polymerase III b subunit, plays a role in DNA replication and repair. Specifically, the NSAID carprofen binds to and inhibits essential interactions of the protein, dubbed the “sliding clamp,” which is a “heavily trafficked” protein-protein interaction hub during DNA replication and repair. This structure also appears in many kinds of bacteria.
“Targeting the bacterial DNA replication machinery is a validated strategy for producing clinically useful antibiotics, as evidenced by the highly successful quinolones, DNA gyrase inhibitors. The bacterial SC (sliding clamp) is an emerging DNA replication target that is yet to be clinically validated,” the authors wrote.
The report appeared in Chemistry & Biology.
The researchers conducted fluorescence polarization competition assays on 20 commercially available NSAIDs to determine inhibitory concentrations. Vedaprofen, bromfenac and carprofen showed the strongest effects, while flufenamic and tolfenamic acids were weaker binders. Next, the NSAIDs were tested for antibacterial activity using standard minimum inhibitory concentrations on 4 species: E. coli, Acinetobacter baylyi, Staphylococcus aureus, and Bacillus subtilis. The Gram-positive species (S. aureus and B. subtilis) showed higher susceptibility to NSAIDs than the Gram-negative species (E. coli and A. baylyi).