Biofilm-specific uptake of a 4-pyridone-based iron chelator by Pseudomonas aeruginosa

Sharareh Houshmandyar, Ian Eggleston, Albert Bolhuis

Research output: Contribution to journalArticlepeer-review

Abstract

Iron is an essential nutrient for virtually all microbes and limiting the concentration of available iron is a potential strategy to be used as an alternative to antibiotic treatment. In this study we analysed the antimicrobial activity of two chelators, specifically 3-hydroxy-1,2-dimethyl-4(1H)-pyridone (deferiprone, DFP), which is clinically approved for the treatment of iron overload disorders, and its 1,2-diethyl homologue, CP94. Both compounds showed moderate activity towards planktonically growing P. aeruginosa cells, and the mechanism of action of these chelators was indeed by limiting the amount of free iron. Surprisingly, the compounds behaved very differently when the cells were grown in biofilms. DFP also showed inhibitory effects on biofilm formation but in contrast, CP94 stimulated this process, in particular at high concentrations. We hypothesised that CP94 behaves as an iron carrier, which was confirmed by our observation that it had antimicrobial synergy with the toxic metals, gallium and copper. This suggests that P. aeruginosa produces a biofilm-specific transport protein that recognises CP94 but not the closely related compound DFP.
Original languageEnglish
Pages (from-to)315-328
Number of pages14
JournalBiometals
Volume34
Early online date11 Jan 2021
DOIs
Publication statusPublished - 1 Apr 2021

Keywords

  • CP94
  • deferiprone (DFP)
  • Biofilm
  • pseudomonas aeruginosa
  • iron chelator

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