Chemists map the iron sensor that rewires Pseudomonas aeruginosa's metabolism

Pseudomonas aeruginosa needs iron, like most living things, and it prefers the reduced, ferrous form, which oxygen readily attacks ^[5]. That chemistry sends ferrous iron into low-oxygen pockets: dental plaque, the lining of the gut, the coating on the lungs of people with cystic fibrosis, the site of a burn wound ^[6]. The bacterium also builds biofilms, coatings that keep antibiotics and the immune system out and help it resist treatment ^[7].

Inside that chemistry sits a two-part sensor. BqsS, embedded in the membrane, reads the iron outside and passes a signal to BqsR in the cell interior, which binds DNA and switches genes on or off ^[8]. The pair was known to control iron uptake, but the UMBC and Oklahoma State team found it does much more ^[2][9]. "What we didn't expect to find was how much the presence of this one ion rewires the bacterium, completely changing all sorts of genes," Smith said ^[10]. "It's got hands in a lot of different pies" ^[11].

The second surprise was internal. BqsR can bind iron itself, and when the cell's iron climbs too high the protein grabs it, lets go of the DNA, and the genes it had been holding open fall silent ^[12]. "It's like a multilayered cake where there are all these different layers of sensing that are happening in this system," Smith said ^[13].

Pseudomonas aeruginosa is a frequent cause of hospital-acquired infection and is growing more resistant to antibiotics ^[1]. The treatment idea follows from one overlap: the same switch that manages iron also controls biofilm formation, so interfering with it might force bacteria out of their coatings and leave them exposed to drugs already on the shelf ^[17]. That is a proposal, not a result. The experiments reported here characterize the proteins; they do not test whether blocking BqsS or BqsR dislodges a biofilm or makes an infection easier to treat. Smith's group plans that next round in living bacteria, along with work on how the two proteins interact, which residues matter most, and how the system answers to oxygen ^[15].

If it holds, the target may reach beyond one organism. Related two-protein systems turn up in other pathogens, including the microbe that causes cholera ^[18].

The work was led by Alexander Paredes, the first UMBC graduate student named an HHMI Gilliam Fellow, now a postdoc at the University of Pennsylvania ^[14].