Tuberculosis is currently the deadliest infectious disease in the world, accounting for approximately 1.3 million deaths annually, where it is primarily an infection of developing countries. Mycobacterium tuberculosis (Mtb) infects the human host via the airway, where its first point of contact are alveolar macrophages (AMs). AMs phagocytose Mtb and translocate it into the lung interstitium, where it forms granulomas and persists latently for decades. The metabolic strategies Mtb uses to survive nutrient deprivation during infection are not well understood. During infection, Mtb is thought to be exposed to excessive levels of carbon monoxide (CO). Macrophages produce CO as a defence mechanism to control bacteria using the enzyme heme oxygenase-1 (HO-1). A recent study demonstrated that the saprophytic soil dweller Mycobacterium smegmatis (Msmeg) can respire atmospheric CO and survive nutrient starved conditions. Msmeg uses a carbon monoxide dehydrogenase (CODH) enzyme that oxidises CO into CO2, and feeds the electrons derived from this process into the respiratory chain, thus generating energy for the cell. Interestingly, Mtb possesses a homologous CODH enzyme, suggesting that it also has the capability to employ CODH for persistence, by oxidising CO produced by macrophages. In this study, we aimed to determine if Mtb is tolerant to CO and capable of utilising CO for prolonged persistence. To investigate these hypotheses, we initially confirmed that the M. tuberculosis strain, mc26206, was tolerant to high levels of CO and was able to grow at a regular rate after adapting to this gas. Preliminary proteomics analysis of CO exposed Mtb showed several proteins were more abundant, including siderophores and dormancy regulated genes. We are currently in the process of constructing deletions of genes thought to be important for CO tolerance. The ability of Mtb to consume CO at an environmentally relevant concentration of 200 ppm was investigated using carbon starved cultures. Contradictory to the earlier findings, we saw that Mtb could not consume CO at this level. Finally, to understand the variations in gene expression under hypoxic and starvation conditions in vitro, we performed RNA sequencing, and transcriptomic analysis is currently underway.