Chemical inhibitors of the Mycobacterium tuberculosis DosRST two-component regulatory system

The purpose of this study was to discover and characterize small molecule inhibitors of the M. tuberculosis DosRST two-component regulatory pathway. The impact of three novel DosRST regulon inhibitors on gene expression was studied in wild type M. tuberculosis and a DosRS mutant strain. Mtb strain CDC1551 or the CDC1551 (DdosRS mutant) was grown in standing T-25 flasks in 8 mL of medium seeded an initial OD of 0.1. Cultures were treated with 40 mM of HC101A, HC102A, HC103A or a DMSO control. Following 6 days of incubation at 37C, RNA was isolated from the bacterial cultures and used for RNA-seq.