Gallium May Have Antibiotic-Like Properties

March 16, 2007

SEATTLE -- The metal gallium -- approved as a drug by the FDA to treat symptomatic hypercalcemia of malignancy -- may also be useful as an antimicrobial, according to researchers here.

SEATTLE, March 16 -- The metal gallium -- approved as a drug by the FDA to treat symptomatic cancer-related hypercalcemia -- may also be useful as an anti-microbial, according to researchers here.

The metal appears to act as a "Trojan horse" to bacteria, taking the place of iron that the microbes need to grow and replicate, said Pradeep K. Singh, M.D., of the University of Washington.

In mice, doses of the metal administered nasally were able to prevent death from a lethal dose of Pseudomonas aeruginosa, the researchers reported online in the Journal of Clinical Investigation, in advance of the April print issue.

When the animals' lungs were pre-treated with iron, however, the life-saving effect of the gallium was not seen, the researchers said.

The work is based on the observation that many bacteria require iron to grow and replicate and that many biological defense systems operate on the principle of denying iron to infective agents.

Gallium, a transition metal that is chemically similar to iron, has been shown to disrupt biological mechanisms that are dependent on iron, Dr. Singh and colleagues noted.

Their animal studies confirm a range of other in vitro experiments, in which the metal was shown to have several activities that might make it useful as an antibiotic, Dr. Singh and colleagues said.

Specifically:

  • In culture, gallium inhibited the growth of P. aeruginosa, including multidrug resistant strains isolated from people with cystic fibrosis.
  • The metal prevented P. aeruginosa from forming biofilms involved in chronic bacterial infections.
  • The metal killed both free-living bacteria and bacteria in biofilms.

To test the effect of the metal in vivo, Dr. Singh and colleagues inoculated mice with P. aeruginosa strain PA103, at a dose that has been shown to cause death rapidly.

Three hours later, the mice were made to inhale a 50-microliter drop of either a gallium compound or a gallium-free vehicle.

Three days after the bacterial infection, all of the control mice had died, but more than 80% of the gallium-treated mice were still living, a difference that was significant at P