The mycobacterial iron‐dependent regulator IdeR induces ferritin ( bfrB ) by alleviating L sr2 repression

Summary Emerging evidence indicates that precise regulation of iron ( F e) metabolism and maintenance of F e homeostasis in M ycobacterium tuberculosis ( Mtb ) are essential for its survival and proliferation in the host. IdeR is a central transcriptional regulator of Mtb genes involved in F e metabolism. While it is well understood how IdeR functions as a repressor, how it induces transcription of a subset of its targets is still unclear. We investigated the molecular mechanism of IdeR ‐mediated positive regulation of bfrB , the gene encoding the major F e‐storage protein of Mtb . We found that bfr B induction by F e required direct interaction of IdeR with a DNA sequence containing four tandem IdeR ‐binding boxes located upstream of the bfr B promoter. Results of in vivo and in vitro transcription assays identified a direct repressor of bfr B , the histone‐like protein L sr2. IdeR counteracted L sr2‐mediated repression in vitro , suggesting that IdeR induces bfrB transcription by antagonizing the repressor activity of Lsr 2. Together, these results elucidate the main mechanism of bfrB positive regulation by IdeR and identify Lsr 2 as a new factor contributing to F e homeostasis in mycobacteria.