The <i>Mycobacterium tuberculosis</i> Pup-proteasome system regulates nitrate metabolism through an essential protein quality control pathway

Significance The proteasome is required for the full virulence of Mycobacterium tuberculosis . However, the extent of its role as a regulator of bacterial physiology remains unclear. In this work, we demonstrate a function of the proteasome system in maintaining the expression of essential chaperonin genes. This activity by the proteasome is required for M. tuberculosis to use nitrate as a nitrogen source. Furthermore, we identified a specific growth condition that robustly decreases the abundance of pupylated proteins. This observation strongly suggests the presence of a yet-to-be-determined mechanism of control over the Pup-proteasome system in M. tuberculosis that is induced in nitrate.