NEW TUBERCULOSIS DRUG TARGET

Abstract

THE PROTEASOME—the cell’s garbage disposal for proteins—could become a target for new tuberculosis drugs, biologists report. A team led by Carl Nathan of Weill Cornell Medical College has found that some oxathiazolone compounds kill tuberculosis-causing bacteria by selectively inhibiting mycobacterial proteasomes without affecting human proteasomes ( Nature, DOI: 10.1038/nature08357). Mycobacterium tuberculosis is one of the few bacterial species with a proteasome, a cellular machine that degrades proteins that cells have marked for destruction. Proteasomes are found in all eukaryotic cells, including human cells. The antibacterial compounds are the first example of an anti-infective agent that inhibits protein breakdown. Many such drugs block protein synthesis. Earlier, Nathan’s team showed that a proteasome inhibitor used as an anticancer agent kills M. tuberculosis . But that drug was too toxic to be used as an anti-infective agent. “Our goal became to see whether we could exploit subtle differences be...