New Compounds with Potential to Treat Persistent Tuberculosis Identified

New Compounds with Potential to Treat Persistent Tuberculosis Identified

Scientists have discovered several first-in-class compounds that target these hidden infections by attacking a critical process the bacteria use to survive in the hostile environment of the lungs.

The study, was published recently by the journal ACS Chemical Biology

Scientists looked at nearly 40,000 compounds before they uncovered these new, potent inhibitors that attack an enzyme critical to the survival of persistent tuberculosis.

The study identified at least three different structural classes of compounds known as APSR inhibitors active against the bacteria, particularly those multidrug-resistant and extensively drug-resistant strains. The APSR enzyme is essential to the production of reduced sulfur compounds needed to stabilize the cellular environment--and the target of new inhibitors, which aim to kill persistent tuberculosis by disrupting this balance.

"M. tuberculosis infects host macrophages," author 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."


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