O2availability impacts iron homeostasis inEscherichia coli

Abstract

The ferric-uptake regulator (Fur) is an Fe2+-responsive transcription factor that coordinates iron homeostasis in many bacteria. Recently, we reported that expression of theEscherichia coliFur regulon is also impacted by O2tension. 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 O2availability. We found that the intracellular, labile Fe2+pool was higher under anaerobic conditions compared with aerobic conditions, suggesting that higher Fe2+availability drove the formation of more Fe2+-Fur and, accordingly, more DNA binding. O2regulation of Fur activity required the anaerobically induced FeoABC Fe2+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 thefeoABCoperon by ArcA and FNR partially antagonized Fur-mediated repression offeoABCunder 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 O2availability on the levels of active Fur adds a previously undescribed layer of regulation in maintaining cellular iron homeostasis.