Small Molecule Inhibitors of the Bacterioferritin (BfrB)–Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas aeruginosa Cells
| Autor: | Achala N D Punchi Hewage, Joel K. Annor-Gyamfi, Huili Yao, Kevin P. Battaile, Richard A. Bunce, Scott Lovell, Kevin Meraz, Anabel Soldano, Mario Rivera |
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| Rok vydání: | 2020 |
| Předmět: |
inorganic chemicals
0301 basic medicine biology Chemistry Pseudomonas aeruginosa 030106 microbiology Biofilm Bacterioferritin Compartmentalization (psychology) biology.organism_classification medicine.disease_cause Microbiology 03 medical and health sciences Cytosol 030104 developmental biology Infectious Diseases biology.protein medicine Binding site Ferredoxin Bacteria |
| Zdroj: | ACS Infectious Diseases. 7:123-140 |
| ISSN: | 2373-8227 |
| DOI: | 10.1021/acsinfecdis.0c00669 |
| Popis: | Bacteria depend on a well-regulated iron homeostasis to survive adverse environments. A key component of the iron homeostasis machinery is the compartmentalization of Fe3+ in bacterioferritin and its subsequent mobilization as Fe2+ to satisfy metabolic requirements. In Pseudomonas aeruginosa Fe3+ is compartmentalized in bacterioferritin (BfrB), and its mobilization to the cytosol requires binding of a ferredoxin (Bfd) to reduce the stored Fe3+ and release the soluble Fe2+. Blocking the BfrB-Bfd complex in P. aeruginosa by deletion of the bfd gene triggers an irreversible accumulation of Fe3+ 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. |
| Databáze: | OpenAIRE |
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