Medical Daily (06.03.2013)
Kenneth Keiler, professor at Penn State University, and colleagues are developing a new class of antibiotics to target bacteria in a new way. The researchers suggest that the drug may be a new weapon against drug-resistant TB, anthrax, and Shigella.
In 1996, while a graduate student, Keiler discovered a pathway in bacteria that is important in protein creation. The process, called “trans-translation,” helps bacteria keep protein synthesis moving by removing faulty messenger RNA. Keiler hypothesized that a pharmaceutical chemical that could interrupt the process of bacterial production would be able to kill the difficult-to-treat bacteria easily. Also, since the process does not exist in plants, animals, or humans, a specifically targeted chemical would not have significant effects on an individual’s cells. The researchers planned to disturb trans-translation, which affects protein-synthesis and prevents organisms from replicating.
The researchers used high-throughput screening of pharmaceutical compounds, which resulted in testing approximately 663,000 different molecules. They eventually narrowed down the candidate chemicals to 46 candidates that disrupted the trans-translation process in bacteria. Further testing of these chemicals with infectious bacteria showed that one molecule called KKL-35 could be considered “broad-spectrum.” KKL-35 specifically blocked trans-translation. The team investigated the potency of the drug on TB bacteria; it proved to be more than 100 times better at blocking bacterial growth than current antituberculosis drugs. Researchers also tested mutated strains of bacteria for susceptibility to KKL-35. According to Keiler, they found no mutant strains that were resistant to KKL-35. Further tests, including safety tests and animal and human trials, are needed.
The full report, “Small Molecule Inhibitors of Trans-Translation Have Broad-Spectrum Antibiotic Activity,” was published online ahead of print in the journal, Proceedings of the National Academy of Sciences, (2013; doi:10.1073/pnas.1302816110).