Drug-resistant strains of Mycobacterium tuberculosis (Mtb)—the bacterium that causes tuberculosis—are on the rise, and better treatments are needed. Previous research has shown that the isoniazid (INH) and vitamin C work by generating Mtb-killing molecules called reactive oxygen species (ROS), but how that happens wasn’t clear. In a study published on August 24 in the Proceedings of the National Academy of Sciences, Einstein researchers, Sangeeta Tiwari, Ph.D., and William R. Jacobs, Jr., Ph.D., found that INH and vitamin C disrupted a previously unsuspected arginine biosynthesis pathway. They found that disruption of the pathway produces ROS, which quickly sterilizes Mtb in vitro and in mice. Compounds that target enzymes in this pathway could be promising candidates for drugs to neutralize Mtb and prevent it from becoming resistant. Dr. Jacobs is the Leo and Julia Forchheimer Chair in Microbiology and Immunology and a professor of genetics and microbiology and immunology at Einstein. Dr. Tiwari is an associate in Dr. Jacobs’ lab at Einstein.
Posted on: Wednesday, December 05, 2018