Pradeep Singh

Trojan horse.
The antibiotic tobramycin kills outer layers of Pseudomonas aeruginosa biofilms (top, red) but leaves a colony (in green) behind to re-seed an infection. Gallium kills stubborn colonies from the inside out (bottom).

Mighty Metal Vanquishes Super-Bacteria

Bacteria are becoming ever deadlier--thanks in large part to the resistance many strains have developed to conventional antibiotics. A new weapon is needed, and scientists may have found one in the rare metal gallium. According to a new study, a common bacterium easily mistakes the metal for the critical nutrient iron, dying when it eats too much. Because gallium is already an FDA-approved drug, the work could lead to a new class of quick-to-the-market antimicrobials.

As drug-resistant bacteria go, Pseudomonas aeruginosa is an especially frustrating foe. It's the leading cause of death in cystic fibrosis patients; the bug frequently infects slow-healing wounds and grows as tough communities called biofilms on inserted medical devices such as catheters; it also afflicts people with weakened immune systems. But P. aeruginosa has a weakness: a hunger for iron. The bug needs the metal to synthesize DNA, shuttle energy around, and protect itself from poisonous oxidation. Pradeep Singh, a microbiologist and physician at the University of Washington in Seattle, and his colleagues wondered if they could exploit P. aeruginosa's iron craving to beat even the most drug-resistant strains.

The team focused on the silvery metal gallium, whose ions are similar in size and charge to iron but can't perform its vital tasks. When they added just a little gallium to P. aeruginosa colonies on Petri plates, bacteria numbers dropped 1000-fold. Mice also showed promising results: Inhaling a few small doses of gallium per day controlled respiratory infections of P. aeruginosa. Singh cautions that gallium can harm human kidneys when taken intravenously, so it's too early to peg a safe dose in humans. But unlike other antibiotics, the metal doesn't appear to garner resistance in bacteria because its mode of attack is so broad. That makes it an attractive alternative to current antimicrobials, he notes. The team reports its findings online today in The Journal of Clinical Investigation.

Daniel Hassett, a microbiologist at the University of Cincinnati College of Medicine, believes Singh and his colleagues are on to something. "I think this is exciting work in the context of a new, novel antimicrobial," he says. Gallium is already used to treat high calcium levels in the blood caused by cancer, he notes, and that could speed its course through drug trials.

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