The iron-chelator, N,N’-bis (2-hydroxybenzyl) ethylenediamine-N,N’-diacetic acid is an effective colistin adjunct against clinical strains of biofilm-dwelling Pseudomonas aeruginosa

Karla Mettrick*, Karl Hassan, Iain Lamont, David Reid

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Targeting the iron requirement of Pseudomonas aeruginosa may be an effective adjunctive for conventional antibiotic treatment against biofilm-dwelling P. aeruginosa. We, therefore, assessed the anti-biofilm activity of N,N’-bis (2-hydroxybenzyl) ethylenediamine-N,N’-diacetic acid (HBED), which is a synthetic hexadentate iron chelator. The effect of HBED was studied using short-term (microtitre plate) and longer-term (flow-cell) biofilm models, under aerobic, anaerobic, and microaerobic (flow-cell) conditions and in combination with the polymyxin antibiotic colistimethate sodium (colistin). HBED was assessed against strains of P. aeruginosa from patients with cystic fibrosis and the reference strain PAO1. HBED inhibited growth and biofilm formation of all clinical strains under aerobic and anaerobic conditions, but inhibitory effects against PAO1 were predominantly exerted under anaerobic conditions. PA605, which is a clinical strain with a robust biofilm-forming phenotype, was selected for flow-cell studies. HBED significantly reduced biomass and surface coverage of PA605, and, combined with colistin, HBED significantly enhanced the microcolony killing effects of colistin to result in almost complete removal of the biofilm. HBED combined with colistin is highly effective in vitro against biofilms formed by clinical strains of P. aeruginosa.

Original languageEnglish
Article number144
Pages (from-to)1-14
Number of pages14
JournalAntibiotics
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 2020
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Biofilm
  • Cystic fibrosis
  • HBED
  • Iron chelation
  • Pseudomonas aeruginosa

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