Nature Med. 15, 537–544 (2009)

High doses of the drug ethionamide cause side effects that limit its use against tuberculosis. Now, Alain Baulard of the Pasteur Institute in Lille, France, and his colleagues report that blocking the regulatory protein EthR in Mycobacterium tuberculosis boosts ethionamide's activity, markedly reducing the necessary dose of the drug.

EthR controls production of the bacterial enzyme EthA, which activates ethionamide. Baulard's team designed and screened a drug library for compounds likely to block EthR (one example pictured) and thereby release its control on EthA. One such compound, BDM31343, bound to EthR and rendered ethionamide three times more potent against tuberculosis in mice.