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UC research discovers new way to fight antibiotic-resistant bacteria

March 19, 2007

CINCINNATI—Research by a team at the University of Cincinnati (UC) has helped in the discovery of a new way to fight antibiotic-resistant bacteria, responsible for preventing treatment of lung infections in patients with cystic fibrosis and life-threatening cases of pneumonia.

A study done in collaboration with the University of Washington found that using a metallic "Trojan Horse"—tricking the bacteria by replacing the iron they need from their environment with the metallic element gallium—can kill bacteria.

The study will appear in the April 2 issue of the Journal of Clinical Investigation.

The UC team headed by Bradley Britigan, MD, chairman of the internal medicine department at UC and staff physician at the Cincinnati Department of Veterans Affairs Medical Center, found substituting gallium for iron would prevent the bacteria from growing.

"All bacteria need iron from their host environment to grow and replicate," said Britigan, coauthor of the study. "Without enough iron, the organism has a much more difficult time forming 'biofilms,' protective skins that form around colonies of bacteria and help them maintain chronic infections."

Rather than trying to find a new way to attack and kill off bacteria, researchers used gallium, which resembles iron but cannot be used by bacteria, to create an inhospitable environment.

"Cells take up gallium as they would iron and insert it into enzymes," said Britigan. "But when they do this, the enzymes stop working and the bacteria don't grow."

In both cell cultures and in mice, the gallium treatment killed bacteria and prevented the formation of biofilms.

Britigan says he believes the use of gallium could be a new way to prevent or treat lung infections, especially in cystic fibrosis patients.

"Treatment of these infections has become more difficult in recent years due to the development of resistance to conventional antibiotics," he said.

Gallium is already FDA approved for treating high calcium levels in cancer patients, and research is under way to determine whether it can be used to fight tuberculosis and other lung infections.

"We already knew it could be used against cancer cells," Britigan said. "But until recently, no one has looked at it as a means for treating bacterial infections. We want to examine possible mechanisms of resistance that could develop in bacteria, extend the animal models to look at possible toxicity if used in humans, and find a better way to administer the drug to humans that would be more convenient and pose less potential for toxicity."

University of Cincinnati