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Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), is the main cause of death due to an infectious disease. After more than 100 years of the discovery of Mtb, clinicians still face difficulties finding an effective treatment for the increasing number of drug-resistant cases. The difficulties in the clinical setting can be related to the slow pace at which the understanding of the physiology of this bacterium has occurred. Mtb is distinct from other microorganisms not only due to its slow growth and difficulties to study in the laboratory, but also due to its inherent physiology such as its complex cell envelope and its metabolic pathways. Understanding the physiology of drug susceptible and resistant Mtb strains is crucial for the design of an effective chemotherapy against TB. This chapter will review the mycobacterial cell envelope and major physiological pathways together with recent discoveries in Mtb drug resistance through different “omics” disciplines.

The Physiology of Mycobacterium tuberculosis in the Context of Drug Resistance: A System Biology Perspective