RNA-seq of Mycobacterium tuberculosis H37Rv treated with alpibectir or a combination of alpibectir and ethionamide against untreated controls
Alpibectir potentiates the activity of ethionamide and prothionamide, which are second-line antibiotics used for tuberculosis treatment. Both are prodrugs whose antibacterial activity depends on bioactivation by oxidases, including the Baeyer-Villiger monooxygenase MymA. Alpibectir binds the transcriptional regulator VirS, increasing MymA expression and potentiating Eto and Pto activity. To determine the transcriptional response of M. tuberculosis to alpibectir, we treated cultures at an optical density of 0.7 with alpibectir 0.1 mg/L for 24 h. Alternatively, we determined the transcriptional response of cultures first treated with alpibectir 0.1 mg/L for 20 h followed by ethionamide 2 mg/L for 4 h. Untreated controls (DMSO 0.1%) were included.