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Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas aeruginosa Cells.


ABSTRACT: 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.

SUBMITTER: Soldano A 

PROVIDER: S-EPMC7802073 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-Embedded <i>Pseudomonas aeruginosa</i> Cells.

Soldano Anabel A   Yao Huili H   Punchi Hewage Achala N D AND   Meraz Kevin K   Annor-Gyamfi Joel K JK   Bunce Richard A RA   Battaile Kevin P KP   Lovell Scott S   Rivera Mario M  

ACS infectious diseases 20201203 1


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<sup>3+</sup> in bacterioferritin and its subsequent mobilization as Fe<sup>2+</sup> to satisfy metabolic requirements. In <i>Pseudomonas aeruginosa</i> Fe<sup>3+</sup> is compartmentalized in bacterioferritin (BfrB), and its mobilization to the cytosol requires binding of a ferredoxin (Bfd) to reduce the stored Fe<sup>3+</sup> a  ...[more]

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