The Scripps Research Institute (TSRI)
researchers have discovered compounds that may be the future of treating tuberculosis (TB).
TB was been one of the leading killers throughout history; 1.5 million people die from it every year, and 2 billion people have latent TB (Mycobacterium tuberculosis) infections. This means that the bacteria hides within cells until it can fully develop and take over its host.
The new compounds can be used to target latent TB through attacks on important processes that TB uses to live within the lungs.
“With the help of Scripps Florida’s high-throughput screening facility, we looked at nearly 40,000 compounds before we uncovered these new, potent inhibitors that attack an enzyme critical to the survival of persistent tuberculosis,” Kate Carroll, a TSRI associate professor, said. “Thanks to our collaborators in India with access to drug-resistant patient isolates, we were able to demonstrate that these compounds also show excellent activity against multidrug resistant (MDR) and extensively drug-resistant (XDR) strains, in addition to the standard laboratory reference strain, H37Rv, of M. tuberculosis.”
Latent TB is particularly difficult to treat.
“M. tuberculosis infects host macrophages,” Carroll said. “These immune cells produce high levels of reactive oxygen and reactive nitrogen species (RONS), which cause oxidative damage to biomolecules, such as lipids, proteins and DNA. For this reason, M. tuberculosis depends heavily upon the production of RONS-neutralizing reduced sulfur compounds, including mycothiol and cysteine. This is why the reductive sulfur assimilation pathway is such a powerful target. Once you reduce the level of reduced sulfur compounds, you eliminate a central mechanism that all bacteria, including M. tuberculosis, use to survive host defense systems.”
