Figure 4

Metabolic Persister Genes (MPGs) in the metabolism of Mtb A) Bi-phasic killing and emergence of persisters upon drug exposure; B) Directional re-routing of metabolic fluxes resulting in the adaptation of the bacterium and the emergence of persiters; C) SBSM illustrating the metabolite and reaction connectivity to inhA, the target of Isoniazid; D) Loss of metabolic information in terms of metabolites, genes and reaction following inhA knock-out; E) Gain of function following inhA knock-out showing persister metabolites (PM), persister genes (MPGs) and persister reactions (PR); F-G) Gene expression status of 60 MPG's on treatment with Isoniazid at 1 μg/ml for 2 hr and 6 hr in vivo H) Transcriptional control of 60 MPGs I) Expression status of nadA ~ E operon on treatment with Isoniazid at 1 μg/ml for 2 hr and 6 hr in vivo.