RNA Sequencing of macrophages harboring redox-diverse Mycobacterium tuberculosis.

The ability of Mycobacterium tuberculosis (Mtb) to tolerate antibiotics is a major impediment in the treatment of tuberculosis. This antibiotic tolerance is influenced by the host cells in which the bacteria reside, as Mtb senses host cues, and the bacterial response can provide an enhanced ability to withstand anti-TB drugs. Previouslyt, we have shown that Mtb exhibits redox heterogeneity in terms of its mycothiol redox potential (EMSH) giving rise to three broad subpopulations EMSH-reduced, EMSH-basal, and EMSH-oxidized Mtb specifically inside the macrophages. Among these, the EMSH-reduced Mtb exhibit enahnced tolerance to several anti-TB drugs while the EMSH-basal and EMSH-oxidized subpopulations are more susceptible. In this study, we explored the transcriptomic level differences between macrophages that harbor the antibiotic tolerant Mtb and those harboring antibiotic susceptible Mtb to get a mechanistic understanding of host factors that influence drug tolerance in intracellular Mtb. Overall design: RNA-Seq of bone marrow-derived macrophages harboring different Mtb subpopulations 24 hours post infection. The study involves four different subpopulations- uninfected, bystanders, macrophages harboring EMSH-reduced Mtb, EMSH-oxidized Mtb. All samples are assessed in biological triplicates.