Control of iron homeostasis in corynebacterium glutamicum by a hierarchical regulatory network

Iron is an essential trace element for nearly all organisms as it participates in major biological processes, but on the other hand it poses problems of poor solubility and toxicity. Therefore, many organisms have evolved sophisticated mechanisms to ensure sufficient but not excess levels of intracellular iron. In Corynebacterium diphtheriae the transcriptional regulator DtxR in complex with Fe$^{2+}$ represses transcription of genes involved in iron acquisition under iron excess. In this work the control of iron homeostasis on the transcriptional level was investigated in the Gram-positive soil bacterium Corynebacterium glutamicum, a nonpathogenic relative of C. diphtheriae. In C. glutamicum DtxR directly regulates transcription of about 60 genes involved in iron uptake, iron storage and synthesis of iron sulfur clusters in response to iron availability. The majority of these genes are repressed by DtxR and encode high affinity iron uptake systems, such as siderophore ABC transporters, siderophore binding proteins as well as heme transport systems and heme oxygenase. On the other hand, DtxR seems to act as a direct activator of the iron storage proteins ferritin and Dps under conditions of sufficient iron supply. These results clearly emphasize DtxR as the master regulator of iron-dependent gene expression in C. glutamicum. In studies with a dtxR deletion mutant an increased induction rate of the CGP3 prophage was observed. Subsequently, it was shown that this prophage is induced spontaneously not only in this mutant but also in a small fraction of C. glutamicum wild type cells (