Economic Times (01.28.2014)
Aids Weekly Plus
The Economic Times reported on a study of antibiotics called spectinamides that showed promising results in trials with drug-resistant TB in mice. Researchers from St. Jude Children’s Research Hospital in the United States changed the chemical structure of the antibiotic spectinomycin, which does not work against TB, to create spectinamides. The researchers used structure-based design to re-engineer how spectinomycin binds to the part of the cell called the ribosome. Spectinamides disrupt the function of the ribosome, which is responsible for protein synthesis. Since no other anti-TB drug binds to that site on the ribosome, spectinamides can be used with other medications.
In trials with mice infected with active and chronic TB, the researchers found that one version of the new drug, an analog called 1599, was good or better than the usual anti-TB drugs at reducing TB bacteria in the lungs. Also, the analog caused no serious adverse reactions. The researchers tested 1599 and two other analogs on TB-infected mice. The three analogs bound the ribosome tightly and were more successful at avoiding a TB resistance mechanism called efflux, by which the TB bacteria uses the efflux pumps to remove drugs and other threats from the cell before they can work. The drugs were effective against multidrug-resistant TB strains growing in the laboratory.
Richard Lee, of the St. Jude Department of Chemical Biology and Therapeutics and the corresponding author of the study, noted that the study illustrated how classic antibiotics from natural products can be reengineered to make semi-synthetic compounds to fight drug resistance.
The full report, “Spectinamides: A New Class of Semisynthetic Antituberculosis Agents That Overcome Native Drug Efflux,” was published online in the journal Nature Medicine (2014; doi:10.1038/nm.3458).