| Iron is an essential metal for the survival of most living organisms. Many bacteria have elaborate systems to maintain iron homeostasis and have iron-dependent transcriptional control mechanisms of iron acquisition systems as well as iron storage. Iron acquisition is particularly important for pathogenic bacteria, as the human body has extremely low quantities of available ferrous iron, while the rest of the iron is in the ferric state and bound to proteins such as ferritin, transferrin and heme. Bacterial infections can also trigger a state of hypoferremia in the host that further sequesters available iron needed for bacterial growth.; The goal of this work was to provide evidence that Mycobacterium tuberculosis, the etiological agent of tuberculosis, requires iron during infections of human macrophages and mice. M. tuberculosis genes were identified whose transcription was regulated by the iron-responsive regulator, IdeR. This was accomplished by a searching the M. tuberculosis genome for DNA sequences that resembled the binding site of DtxR, a functional and structural homolog of IdeR from Corynebacterium diphtheriae . The interaction of IdeR with these identified binding sites and the transcription of these genes in vitro and in vivo was analyzed. These results indicated that IdeR is a pleiotropic regulator of genes encoding proteins such as those involved iron acquisition (siderophores), iron storage (bacterioferritin), and synthesis of amino acids, murein and lipids. The transcription of many of these genes was upregulated during growth in an iron limited medium, as well as during an M. tuberculosis infection of human macrophages and mice. This work also analyzes the role of IdeR as an activator of bfrA (bacterioferritin) transcription. |
