FIGURE 1.

The metabolic capacity of M. tuberculosis is critical to understanding key features of mycobacterial pathogenicity, which include (i) long-term coevolution with humans, (ii) the ability to persist for months to decades in a subclinical state, (iii) inertness to clearance by the host immune response or eradication by antibiotics, (iv) the requirement for extended duration combination therapy to effect symptom-free cure and, linked to that, (v) the difficulties inherent in developing new drugs and combination regimens to accelerate therapy, as well as (vi) the capacity to acquire—and adapt to—multiple drug resistance mutations without incurring a crippling fitness cost.