Assessment of Structural Features of the Pseudomonas Siderophore Pyochelin Required for Its Ability to Promote Oxidant-Mediated Endothelial Cell Injury

We previously showed that iron chelated to the Pseudomonas aeruginosa siderophore pyochelin enhances oxidant-mediated injury to pulmonary artery endothelial cells by catalyzing hydroxyl radical (HO•) formation. Therefore, we examined pyochelin structural/chemical features that may be important in this process. Five pyochelin analogues were examined for (i) capacity to accentuate oxidant-mediated endothelial cell injury, (ii) HO• catalytic ability, (iii) iron transfer to endothelial cells, and (iv) hydrophobicity. All compounds catalyzed similar HO• production, but only the hydrophobic ones containing a thiazolidine ring enhanced cell injury. Transfer of iron to endothelial cells did not correlate with cytotoxicity. Finally, binding of Fe3+ by pyochelin led to Fe2+ formation, perhaps explaining how Fe3+–pyochelin augments H2O2-mediated cell injury via HO• formation. The ability to bind iron in a catalytic form and the moleculeʹs thiazolidine ring, which increases its hydrophobicity, are key to pyochelinʹs cytotoxicity. Reduction of Fe3+ to Fe2+ may also be important.