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DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs

Journal Article


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Abstract


  • Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III β subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase α subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp.

Publication Date


  • 2014

Citation


  • Yin, Z., Wang, Y., Whittell, L. R., Jergic, S., Liu, M., Harry, E., Dixon, N. E., Kelso, M. J., Beck, J. L. & Oakley, A. J. (2014). DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs. Chemistry and Biology, 21 (4), 481-487.

Scopus Eid


  • 2-s2.0-84899640878

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2703&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1685

Number Of Pages


  • 6

Start Page


  • 481

End Page


  • 487

Volume


  • 21

Issue


  • 4

Abstract


  • Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III β subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase α subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp.

Publication Date


  • 2014

Citation


  • Yin, Z., Wang, Y., Whittell, L. R., Jergic, S., Liu, M., Harry, E., Dixon, N. E., Kelso, M. J., Beck, J. L. & Oakley, A. J. (2014). DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs. Chemistry and Biology, 21 (4), 481-487.

Scopus Eid


  • 2-s2.0-84899640878

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=2703&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1685

Number Of Pages


  • 6

Start Page


  • 481

End Page


  • 487

Volume


  • 21

Issue


  • 4