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Methodologies for Studying B. subtilis Biofilms as a Model for Characterizing Small Molecule Biofilm Inhibitors
Published on: October 9, 2016
Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-Embedded Pseudomonas
Anabel Soldano1, Huili Yao1, Achala N D Punchi Hewage2
1Department of Chemistry, Louisiana State University, 232 Choppin Hall, Baton Rouge, Louisiana 70803, United States.
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.
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