Scientists find possible treatment for persistent tuberculosis
The treatments use the compounds to target hidden TB infections. The compounds destroy an important process that the virus uses to live within the lungs.
TB causes approximately 1.5 million deaths every year and a significant number of the cases, an estimated 2 billion, of actually latent TB infections, which live inside cell aggregates in a latent form until it can fully develop.
"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 Scripps Research Institute 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 and extensively drug-resistant strains, in addition to the standard laboratory reference strain, H37Rv, ofM. tuberculosis."
TB is notoriously 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."