Inhibiting Iron Mobilization from Bacterioferritin in Pseudomonas aeruginosa Impairs Biofilm Formation Irrespective of Environmental Iron Availability

[Image: see text] Although iron is essential for bacteria, the nutrient presents problems of toxicity and solubility. Bacteria circumvent these problems with the aid of iron storage proteins where Fe(3+) is deposited and, when necessary, mobilized as Fe(2+) for metabolic requirements. In Pseudomonas aeruginosa, Fe(3+) is compartmentalized in bacterioferritin (BfrB), and its mobilization as Fe(2+) requires specific binding of a ferredoxin (Bfd) to reduce the stored Fe(3+). Blocking the BfrB-Bfd complex leads to irreversible iron accumulation in BfrB and cytosolic iron deprivation. Consequently, given the intracellular iron sufficiency requirement for biofilm development, we hypothesized that blocking the BfrB-Bfd interaction in P. aeruginosa would impair biofilm development. Our results show that planktonic and biofilm-embedded cells where the BfrB-Bfd complex is blocked exhibit cytosolic iron deficiency, and poorly developed biofilms, even in iron-sufficient culture conditions. These results underscore inhibition of the BfrB-Bfd complex as a rational target to dysregulate iron homeostasis and possibly control biofilms.