As scientists get creative in their search for new antibiotics for treating bacterial infections, an accidental finding has opened up a new route for research. In a new study, published in the journal Chemistry & Biology, researchers describe how common pain relievers may help fight antibiotic-resistant bacteria.
The pain killers that the researchers, from the University of Wollongong in Australia, stumbled upon was carprofen, a non-steroidal anti-inflammatory drug (NSAID) used in veterinary offices. They accidentally discovered the NSAID’s potential when developing an antibacterial agent that blocked activation of a specific protein responsible for DNA replication and repair.
“We were developing inhibitors of a specific protein in bacteria called the DNA clamp, which is essential to ensure DNA replication and cell proliferation,” said the paper’s lead author Aaron Oakley, an associate professor at Wollongong University in Australia, in a press release. “These sliding DNA clamps, which are conserved across bacterial species, sit on the DNA like a ring to prevent other proteins, which are essential for DNA replication and repair, from wandering off. While testing specific compounds that would bind to the clamp and prevent it from interacting with its binding partners, we noticed that one compound had a similar molecular structure to carprofen.”
They then tested a total of 20 anti-inflammatories on the DNA clamps of E. coli, Acinetobacter baylyi, Staphylococcus aureus, and Bacillus subtillis. They found that carprofen and vedaprofen — also a veterinary painkiller — as well as bromfenac, an ophthalmic solution, completely blocked DNA replication in E. coli. Their effectiveness among the rest of the bacteria changed with each species but whichever drugs were best able to inhibit the DNA clamp also killed the bacteria the best. Still, they were apprehensive to call the results conclusive.
“The fact that the bacteria-killing effect of the anti-inflammatory drugs is different from conventional drugs means that the NSAIDs could be developed into new kinds of antibiotics that are effective against so-called superbugs,” Oakley said in a statement. Antibiotic resistance has been a growing issue due to doctors prescribing antibiotics unnecessarily, and their increased use on farms and in animals. But although the study’s findings are promising, using NSAIDs to develop antibiotics is still a long way off.
“Given the strong structural biology in this paper and the established in vitro assays,” Thomas Keating, a principal scientist at AstraZeneca Infection Innovative Medicines in Massachusetts, told The Scientist, “the tools are certainly present to conduct a rational, structure-based drug design program.”
Source: Yin Z, Whittel L, Jergic S, et al. DNA Replication Is the Target for the Antibacterial Effects of Nonsteroidal Anti-Inflammatory Drugs. Chemistry & Biology. 2014.