RNA Sequencing of intra-phagosomal Mtb populations

ABSTRACT: Heterogeneity of host cells as well as bacteria residing within them has been known to induce drug tolerance in pathogens. In Mycobacterium tuberculosis, particularly, drug tolerance within host is a major hurdle in the path to attain a sterlising cure. Reports have shown how residence of Mtb within macrophages makes the pathogen refractory to anti-TB therapy. However, the mechanisms responsible for induction of tolerance to antibiotics, particularly in resting macrophages where Mtb continues to actively replicate, is yet to be deciphered. Reports have suggested that heterogeneity induced in Mtb by cues sensed in the host environment could be a contributing factor to drug tolerance. With regard to this, differences in redox physiology of intra-macrophage Mtb (mid-point potential of the major cytosolic redox buffer in Mtb, mycothiol- EMSH) have been shown to play a role in influencing antibiotic-mediated killing. In this study, we have attempted to analyse the trascriptomic profiles of individual redox sub-populations of Mtb from within macrophages- viz., the EMSH-reduced bacteria with mid-point potential ranging between -285 and -310 mV, shown to be most refractory to killing by front-line anti-TB antibiotics inside macrophages, as well as EMSH-basal bacteria with mid-point potential ranging between -270 and -280 mV, with a much higher degree of antibiotic susceptibility within macrophages. Analysing gene expression level differences between these bacterial sub-populations would help in providing a mechanistic understanding of drug tolerance in Mtb, bred from phenotypic heterogeneity in the pathogen.

ORGANISM(S): Mycobacterium tuberculosis H37Rv

PROVIDER: GSE123267 | GEO | 2019/09/13

REPOSITORIES: GEO