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Publication Abstract from PubMed

Bacteria depend on a well-regulated iron homeostasis to survive adverse environments. A key component of the iron homeostasis machinery is the compartmentalization of Fe(3+) in bacterioferritin and its subsequent mobilization as Fe(2+) to satisfy metabolic requirements. In Pseudomonas aeruginosa Fe(3+) is compartmentalized in bacterioferritin (BfrB), and its mobilization to the cytosol requires binding of a ferredoxin (Bfd) to reduce the stored Fe(3+) and release the soluble Fe(2+). Blocking the BfrB-Bfd complex in P. aeruginosa by deletion of the bfd gene triggers an irreversible accumulation of Fe(3+) in BfrB, concomitant cytosolic iron deficiency and significant impairment of biofilm development. Herein we report that small molecules developed to bind BfrB at the Bfd binding site block the BfrB-Bfd complex, inhibit the mobilization of iron from BfrB in P. aeruginosa cells, elicit a bacteriostatic effect on planktonic cells, and are bactericidal to cells embedded in mature biofilms.

Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas aeruginosa Cells.,Soldano A, Yao H, Punchi Hewage AND, Meraz K, Annor-Gyamfi JK, Bunce RA, Battaile KP, Lovell S, Rivera M ACS Infect Dis. 2020 Dec 3. doi: 10.1021/acsinfecdis.0c00669. PMID:33269912^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.