Substrate induction of siderophore transport in Bacillus subtilis mediated by a novel one-component regulator

When iron is scarce, Bacillus subtilis expresses genes involved in the synthesis and uptake of the siderophore bacillibactin (BB) and uptake systems to pirate other microbial siderophores. Here, we demonstrate that transcriptional induction of the feuABCybbA operon, encoding the Fe-BB uptake system, is mediated by Btr (formerly YbbB), which is encoded by the immediately upstream gene. Btr contains an AraC-type DNA binding domain fused to a substrate binding protein (SBP) domain related to FeuA, the SBP for Fe-BB uptake. When cells are iron-limited, the Fur-mediated repression of btr is relieved and Btr binds to a conserved direct repeat sequence adjacent to feuA to activate transcription. If BB is present, Btr further activates feuA expression. Btr binds with high affinity to both apo-BB and Fe-BB, and the resulting complex displays a significantly increased efficacy as a transcriptional activator relative to Btr alone. Btr can also activate transcription in response to the structurally similar siderophore enterobactin, although genetic analyses indicate that the two siderophores make distinct interactions with the Btr substrate binding domain. Thus, the FeuABC transporter is optimally expressed under conditions of iron starvation, when Fur-mediated repression is relieved, and in the presence of its cognate substrate.