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Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420

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Science  17 Mar 2017:
Vol. 355, Issue 6330, pp. 1206-1211
DOI: 10.1126/science.aag1006

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Countering TB prodrug resistance

The arsenal of antibiotics for treating tuberculosis (TB) contains many prodrugs, such as ethionamide, which need activation by normal metabolism to release their toxic effects. Ethionamide is potentiated by small molecules. Blondiaux et al. screened for more potent analogs and identified a lead compound called SMARt-420. This small molecule inactivates a TetR-like repressor, EthR2, and boosts ethionamide activation. SMARt-420 successfully promoted clearance of multidrug-resistant strains of Mycobacterium tuberculosis from the lungs of mice.

Science, this issue p. 1206