Abstract
The ferric-uptake regulator (Fur) is an Fe(2+)-responsive transcription factor that coordinates iron homeostasis in many bacteria. Recently, we reported that expression of the Escherichia coli Fur regulon is also impacted by O(2) tension. Here, we show that for most of the Fur regulon, Fur binding and transcriptional repression increase under anaerobic conditions, suggesting that Fur is controlled by O(2) availability. We found that the intracellular, labile Fe(2+) pool was higher under anaerobic conditions compared with aerobic conditions, suggesting that higher Fe(2+) availability drove the formation of more Fe(2+)-Fur and, accordingly, more DNA binding. O(2) regulation of Fur activity required the anaerobically induced FeoABC Fe(2+) uptake system, linking increased Fur activity to ferrous import under iron-sufficient conditions. The increased activity of Fur under anaerobic conditions led to a decrease in expression of ferric import systems. However, the combined positive regulation of the feoABC operon by ArcA and FNR partially antagonized Fur-mediated repression of feoABC under anaerobic conditions, allowing ferrous transport to increase even though Fur is more active. This design feature promotes a switch from ferric import to the more physiological relevant ferrous iron under anaerobic conditions. Taken together, we propose that the influence of O(2) availability on the levels of active Fur adds a previously undescribed layer of regulation in maintaining cellular iron homeostasis.