Chemical inhibition of the Mycobacterium tuberculosis DosRST two-component regulatory system by targeting sensor kinase heme and response regulator DNA binding

The purpose of this study was to characterize the mechanism of action of the small molecules HC104 and HC106 Overall design: Mtb strain CDC1551 or the DosR mutant was grown at 37ºC in T-25 vented, standing tissue culture flasks in 8 mL of buffered 7H9 medium to an OD600 of 0.1. Cultures were subsequently treated with 40 µM HC104A or HC106A. For the control, cultures treated with an equal amount of DMSO. Following a 6 day incubation period, total bacterial RNA was extracted, quality controlled and sequenced. Each treatment was repeated with two independent (biological) replicates.