Mobilization of iron stored in bacterioferritin, a new target for perturbing iron homeostasis and developing antibacterial and antibiofilm molecules
Document Type
Article
Publication Date
10-1-2023
Abstract
Antibiotic resistance is a global public health threat. The care of chronic infections is complicated by bacterial biofilms. Biofilm embedded cells can be up to 1000-fold more tolerant to antibiotic treatment than planktonic cells. Antibiotic tolerance is a condition which does not involve mutation and enables bacteria to survive in the presence of antibiotics. The antibiotic tolerance of biofilm-cells often renders antibiotics ineffective, even against strains that do not carry resistance-impairing mutations. This review discusses bacterial iron homeostasis and the strategies being developed to target this bacterial vulnerability, with emphasis on a recently proposed approach which aims at targeting the iron storage protein bacterioferritin (Bfr) and its physiological partner, the ferredoxin Bfd. Bfr regulates cytosolic iron concentrations by oxidizing Fe2+ and storing Fe3+ in its internal cavity, and by forming a complex with Bfd to reduce Fe3+ in the internal cavity and release Fe2+ to the cytosol. Blocking the Bfr-Bfd complex in P. aeruginosa cells causes an irreversible accumulation of Fe3+ in BfrB and simultaneous cytosolic iron depletion, which leads to impaired biofilm maintenance and biofilm cell death. Recently discovered small molecule inhibitors of the Bfr-Bfd complex, which bind Bfr at the Bfd binding site, inhibit iron mobilization, and elicit biofilm cell death.
Publication Source (Journal or Book title)
Journal of Inorganic Biochemistry
Recommended Citation
Rivera, M. (2023). Mobilization of iron stored in bacterioferritin, a new target for perturbing iron homeostasis and developing antibacterial and antibiofilm molecules. Journal of Inorganic Biochemistry, 247 https://doi.org/10.1016/j.jinorgbio.2023.112306