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

Abstract

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.