Quantitative proteomic analysis of the response of Pseudomonas aeruginosa to gallium maltolate exposure

The semi-metallic element gallium was initially introduced therapeutically as a diagnostic tool for the detection of cancerous tissue and was subsequently incorporated into a number of gallium-based anticancer agents. Gallium-based drugs have since been repurposed as antibacterial therapies and have shown significant potential as an alternative treatment option against resistant pathogens. The activity of gallium (Ga3+) is a result of its chemical similarity to ferric iron (Fe3+) and substitution into iron-dependent pathways. Gallium is incapable of reducing to the 2+ form in typical physiological environments and therefore inhibits iron metabolism vital for bacterial growth. Gallium maltolate (GaM) is an enhanced, novel 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 opportunistic pathogen Pseudomonas aeruginosa. Analysis of the changes of the P. aeruginosa proteome in response to GaM exposure revealed how inadequate supplies of iron within the cell may explain the increase in abundance of proteins involved in iron acquisition and storage. A key finding of this study however, was the decreased abundance of proteins associated with quorum-sensing and swarming motility. These processes are a fundamental component of bacterial virulence and dissemination and hence explain a potential role of GaM in the treatment of P. aeruginosa infection.