Elucidating the effects of the macrophage environment on the efficacy of anti-mycobacterial drugs

We examined the transcriptional responses of intracellular M. tuberculosis exposed to different front-line drugs during macrophage infection. Our data reveal that Mtb experiences amplification of multiple host-derived pressures following drug exposure. The stresses from the host environment have a dominant impact on Mtb gene expression to the extent that the transcriptional profiles cluster according to environment, ie. broth vs host cell, rather than drug. Transcriptional responses of M. tuberculosis to front-line drugs were studied under two environmental conditions: J774 macrophages vs. 7H9 broth, and 4 drugs were examined: INH, RIF, EMB, and PZA.