Several tuberculosis drugs are prodrugs that have to be enzymatically activated during metabolism. Ethionamide is such a drug and is activated by the monooxygenase EthA. EthA is itself regulated by the transcriptional repressor EthR. Here Alain Baulard and his colleagues have designed inhibitors of EthR that boost the antimycobacterial efficacy of ethionamide both in vitro and in vivo. Current therapy with ethionamide requires the use of high doses, often eliciting side effects. Its combination with the EthR repressor should allow lower doses to be used.
- Nicolas Willand
- Bertrand Dirié
- Alain R Baulard
