Regulation of iron homeostasis in Corynebacterium glutamicum

TitleRegulation of iron homeostasis in Corynebacterium glutamicum
Publication TypeBook Chapter
Year of Publication2008
AuthorsFrunzke, J, Bott, M
Book TitleCorynebacteria: genomics and molecular biology
PublisherCaister Academic Press
City Norfolk, UK.

The relevance of iron to corynebacteria was first noticed in the 1930s, when the synthesis of diphtheria toxin by Corynebacterium diphtheriae was shown to be dependent on the iron supply. Meanwhile, the DtxR protein responsible for this regulation has been intensively characterized biochemically. It functions as an intracellular Fe2+ sensor and, when its low-affinity iron-binding site is occupied, as a transcriptional regulator. In C. diphtheriae, several DtxR targets have been identified and thoroughly characterized, but no genome-wide studies were performed yet. In the non-pathogenic Corynebacterium glutamicum, on the other hand, the DtxR regulon has been determined by genome-wide studies including transcriptome comparisons of wild type and dtxR deletion mutants using DNA microarrays. By this approach, more than 50 genes were found to be repressed by DtxR under iron excess, most of which encode proteins involved in iron acquisition, notably several ABC transporters for siderophores. Moreover, genes which are presumably activated by DtxR have been identified, such as iron storage proteins and proteins responsible for iron-sulfur cluster assembly. Three of the target genes repressed by DtxR in C. glutamicum (ripA, cgtR11, cg0527) encode themselves transcriptional regulators. The AraC-type regulator RipA has been shown to repress a set of genes which encode prominent iron proteins of the cell, such as aconitase, succinate dehydrogenase or catalase. In this way, the iron demand of the cell is reduced, possibly allowing prolonged survival under iron limitation. In the case of the response regulator CgtR11, evidence for its involvement in heme utilization has been obtained, whereas the function of Cg0527 is not yet known. In summary, key players of a complex regulatory network controlling iron homeostasis in C. glutamicum have been elucidated in recent years.