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.