Bacteria use sophisticated mechanisms to ensure sufficient iron availability while avoiding oxidative stress caused by unregulated concentrations of Fe2+. Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen which causes infections in immune-compromised patients, encodes two ferritin like molecules, FtnA and BfrB.1 Although, their relative contribution to iron storage in P.aeruginosa was unknown, our recent studies have shown that iron is stored only in BfrB.2 These investigations also showed that a ferredoxin (Bfd) is necessary to mobilize iron from BfrB.1,2 To study the consequences of perturbing the BfrB:Bfd interaction in P. aeruginosa cells, a bfd mutant strain (Δbfd) and a variant harboring an allele encoding for BfrB(L68A/E81A) (bfrBE81A/L68A) were utilized. It was found that in wild type cells the mobilization of iron stored in BfrB requires Bfd. In contrast, in the Δbfd and bfrBE81A/L68A mutant cells, where the BfrB:Bfd interaction is perturbed, iron is irreversibly accumulated in BfrB, which elicit an acute iron starvation phenotype.2 In this study we developed small molecule inhibitors of the BfrB:Bfd interaction. P.aeruginosa cells treated with these small molecule inhibitors reproduce the iron starvation phenotype observed with the genetic mutant.2

Perturbing the BfrB:Bfd interaction of Pseudomonas aeruginosa by chemical and genetic intervention causes irreversible accumulation of iron in BfrB

255th National Meeting (2018)

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