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Nature Medicine

May 4, 2009

Scientists have developed molecules for boosting the efficiency of an antibiotic used to treat tuberculosis, according to research published online this week in Nature Medicine. These new 'booster' drugs enable a small dose of an existing antituberculosis agent to work as well as conventional high dose treatment to fight off the infection.

Current tuberculosis therapy has side effects, which lead to a high risk of noncompliance with the treatment and to the emergence of drug-resistant bacteria.

Several antituberculosis compounds require metabolic activation before they can kill the bacteria. Drugs such as ethionamide, a second-line anti-tuberculosis compound, are activated by a bacterial enzyme known as EthA. The production of EthA is in turn controlled by a transcriptional repressor dubbed EthR.

Alain Baulard and colleagues designed inhibitors of EthR that boost the metabolic activation of ethionamide more than an order of magnitude in culture. In mice infected with tuberculosis, one of these inhibitors enabled a small dose of ethionamide to lessen the infection as efficiently as the conventional high-dose treatment. Owing to their boosting effect, the new inhibitors should prompt reconsideration of the use of ethionamide and related compounds as first-line anti-tuberculosis drugs.

DOI:10.1038/nm.1950 | Original article

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