Quantitative proteomic reveals gallium maltolate induces an iron-limited stress response and reduced quorum-sensing in Pseudomonas aeruginosa

J Biol Inorg Chem. 2020 Dec;25(8):1153-1165. doi: 10.1007/s00775-020-01831-x. Epub 2020 Oct 30.


Gallium-based drugs have been repurposed as antibacterial therapeutic candidates and have shown significant potential as an alternative treatment option against drug resistant pathogens. The activity of gallium (Ga3+) is a result of its chemical similarity to ferric iron (Fe3+) and substitution into iron-dependent pathways. Ga3+ is redox inactive in typical physiological environments and therefore perturbs iron metabolism vital for bacterial growth. Gallium maltolate (GaM) is a well-known water-soluble formulation of gallium, consisting of a central gallium cation coordinated to three maltolate ligands, [Ga(Maltol-1H)3]. This study implemented a label-free quantitative proteomic approach to observe the effect of GaM on the bacterial pathogen, Pseudomonas aeruginosa. The replacement of iron for gallium mimics an iron-limitation response, as shown by increased abundance of proteins associated with iron acquisition and storage. A decreased abundance of proteins associated with quorum-sensing and swarming motility was also identified. These processes are a fundamental component of bacterial virulence and dissemination and hence suggest a potential role for GaM in the treatment of P. aeruginosa infection.

Keywords: Antimicrobial; Galleria; Gallium; Iron; Proteomics; Pseudomonas; Stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Iron / metabolism*
  • Organometallic Compounds / pharmacology*
  • Proteomics*
  • Pseudomonas aeruginosa / cytology*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / metabolism
  • Pseudomonas aeruginosa / physiology*
  • Pyrones / pharmacology*
  • Quorum Sensing / drug effects*
  • Stress, Physiological / drug effects*


  • Organometallic Compounds
  • Pyrones
  • gallium maltolate
  • Iron