Mycobacterium tuberculosis DosR is Required for Activity of the P(mbtB) and P(mbtI) Promoters under Hypoxia

Mycobacterium tuberculosis has the ability to survive for extended periods of time under conditions of low oxygen, low pH, low iron and low nutrients. The mycobactins (M. tuberculosis siderophores) play a key role in scavenging iron from the environment and are induced in response to low iron in an IdeR-regulated manner. We demonstrate that the promoters of two mycobactin gene (mbt) operons are also expressed during adaptation to low oxygen, and that this expression is dependent on the DosR regulator. Up-regulation of mbt operons induced by low iron was not DosR-dependent. DosR is a member of a two component regulatory system which responds to oxygen availability. Deletion of the DosR regulator led to increased expression of bacterioferritin and increased capacity to grow under iron depletion. These data provide a link between the mycobacterial response to two conditions likely to be encountered in vivo, low iron and low oxygen.