Iron is an essential micronutrient in bacteria where it underpins fundamental biochemical processes, such as respiration and central metabolism. This project investigated the master regulator of iron homeostasis in bacteria, the Ferric uptake regulator (Fur). Fur is ancient, very highly conserved across the bacterial domain and deeply entangled in bacterial cell physiology. Fur can sense intracellular concentrations of iron and respond to repress or, in some instances, activate target genes to maintain homeostasis. In pathogenic bacteria, many Fur-controlled genes are considered virulence factors.
In this study, we used Chromatin Immunoprecipitation followed by high-throughput sequencing (ChIP-seq) to examine the binding regions of Fur under iron replete and iron limited conditions in the opportunistic pathogen Acinetobacter baumannii. This study identified 139 and 42 binding sites under iron replete and iron limited conditions, respectively, with 41 of these sites were shared across both conditions. Analysis of sequence motifs found from Fur binding sites revealed a 11-15 bp palindromic sequence similar to Fur’s established binding sites in related bacteria. The Fur binding sites were present upstream of many genes involved in iron uptake, but also other functions such as carbon metabolism. Overlaying Fur binding site information on transcriptomic data showing gene expression changes occurring in response to iron suggested that many genes downstream of Fur were under its direct control. The results also suggest that Fur can compete with other global regulators, such as the histone-like repressor protein HNS, upstream of several operons, resulting in alternative gene expression patterns in response to iron. The data revealed the broad regulatory impact of the major iron regulator in an important human pathogen and its interplay with other global regulatory systems.