gallium acetate is a white crystalline substance. It is an important gallium salt with the chemical formula Ga(CH3COO)3. This compound is produced by acetic acid reacting with gallium chloride or nitrate. It is moderately water-soluble and decomposes to gallium oxide, gallium nitride and gallium arsenide when heated above 70 °C. gallium acetate is used in various applications including blue, white and violet LEDs due to its wide band gap.
Gallium is an element with a low boiling point and melting point, but it does not occur in nature as a free metal. It is extracted from bauxite and sphalerite, and used in semiconductor devices for microelectronics and optics.
In this study, we found that the central carbon metabolite acetate enhances the antimicrobial activity of gallium in Pseudomonas aeruginosa. Co-therapy with acetate significantly reduced the number of persister cells and the growth of P. aeruginosa in murine skin infection models. In addition, acetate treatment resulted in the attenuation of virulence factors secreted by P. aeruginosa including elastase, protease, pyocyanin, pyoverdine and phospholipase C, as evidenced by RNA-seq and GC-MS analysis.
To further understand the mechanism of acetate-enhanced Ga(iii) antimicrobial activity, we identified Ga-binding proteins in P. aeruginosa by using competitive gallium-based immobilized metal affinity chromatography (Ga-IMAC). Bacterial cell lysates were pretreated with acetate or a high concentration of Ga(iii) and incubated with a Ga-IMAC resin. The Ga-IMAC binding sites of proteins were determined by analyzing the eluted protein fractions. Interestingly, the presence of acetate significantly increased the Ga uptake by PaRpoB/C, which enhanced the binding of Ga(iii) to the protein and led to the enhancement of its antimicrobial activity.