Autor: |
Anabel, Soldano, Huili, Yao, Achala N D, Punchi Hewage, Kevin, Meraz, Joel K, Annor-Gyamfi, Richard A, Bunce, Kevin P, Battaile, Scott, Lovell, Mario, Rivera |
Rok vydání: |
2020 |
Předmět: |
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Zdroj: |
ACS Infectious Diseases |
ISSN: |
2373-8227 |
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 |
Externí odkaz: |
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