Sequential induction of Fur-regulated genes in response to iron limitation in Bacillus subtilis

Significance Fur is a key regulator of bacterial iron homeostasis and regulates the derepression of iron acquisition systems when iron is limited. However, it is unclear whether Fur-regulated genes are derepressed coordinately or in a sequential manner. Here, we describe a graded response for the Bacillus subtilis Fur regulon as the intracellular iron pool is gradually depleted. Three distinct sets of genes are sequentially expressed, and the induction order can be explained, at least in part, by differences in Fur affinity to its target operator sites. These results provide insights into the distinct roles of Fur target genes and contribute to our understanding of bacterial metalloregulatory systems.