Inhibiting Iron Mobilization from Bacterioferritin in Pseudomonas aeruginosa Impairs Biofilm Formation Irrespective of Environmental Iron Availability
- Authors
- Type
- Published Article
- Journal
- ACS Infectious Diseases
- Publisher
- American Chemical Society
- Publication Date
- Jan 03, 2020
- Volume
- 6
- Issue
- 3
- Pages
- 447–458
- Identifiers
- DOI: 10.1021/acsinfecdis.9b00398
- PMID: 31898890
- PMCID: PMC7076691
- Source
- PubMed Central
- Keywords
- License
- Unknown
Abstract
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 Fe3+ is deposited and, when necessary, mobilized as Fe2+ for metabolic requirements. In Pseudomonas aeruginosa , Fe3+ is compartmentalized in bacterioferritin (BfrB), and its mobilization as Fe2+ requires specific binding of a ferredoxin (Bfd) to reduce the stored Fe3+. 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.