Gallium (Ga) is a semimetallic
element that has demonstrated therapeutic and diagnostic-imaging potential in a number of disease settings, including
cancer and
infectious diseases.
Gallium's
biological actions stem from its ionic radius being almost the same as that of ferric
iron (Fe(3+)), whereby it can replace
iron (Fe) in Fe(3+)-dependent
biological systems, such as bacterial and mammalian Fe transporters and Fe(3+)-containing
enzymes. Unlike Fe(3+), ionic
gallium (Ga(3+)) cannot be reduced, and when incorporated, it inactivates Fe(3+)-dependent reduction and oxidation processes that are necessary for bacterial and mammalian cell proliferation. Most pathogenic bacteria require Fe for growth and function, and the availability of Fe in the host or environment can greatly enhance virulence. We examined whether
gallium maltolate (GaM), a novel formulation of Ga, had antibacterial activity in a thermally injured acute
infection mouse model. Dose-response studies indicated that a GaM dose as low as 25 mg/kg of
body weight delivered subcutaneously was sufficient to provide 100% survival in a lethal P. aeruginosa-infected thermally injured mouse model. Mice treated with 100 mg/kg GaM had undetectable levels of Pseudomonas aeruginosa in their
wounds, livers, and spleens, while the
wounds of untreated mice were colonized with over 10(8) P. aeruginosa CFU/g of tissue and their livers and spleens were colonized with over 10(5) P. aeruginosa CFU/g of tissue. GaM also significantly reduced the colonization of Staphylococcus aureus and Acinetobacter baumannii in the
wounds of thermally injured mice. Furthermore, GaM was also therapeutically effective in preventing preestablished P. aeruginosa
infections at the site of the injury from spreading systemically. Taken together, our data suggest that GaM is potentially a novel
antibacterial agent for the prevention and treatment of
wound infections following thermal injury.