Drug-Resistant Bacteria Defeated by Trojan Horse Strategy

A novel antimicrobial approach can kill bacteria in laboratory experiments and eliminate life-threatening infections in mice by interfering with a key bacterial nutrient, according to a new study.

Researchers at the University of Washington (UW; Seattle, USA), the University of Iowa (Iowa City, USA), and the University of Cincinnati (OH, USA) sought to intensify the stress imposed on microbes by interruption of their iron supply. The researchers achieved this by using gallium, a metal very similar to iron. A critical element in the growth of bacteria, iron is needed by bacteria to enable them to form biofilms (slime-encased colonies of microbes that cause many chronic infections).

The researchers showed that gallium killed microbes, and prevented the formation of biofilms. The gallium's action was intensified in low iron conditions, like those that exist in the human body. Gallium was even effective against strains of Pseudomonas aeruginosa collected from cystic fibrosis (CF) patients that were resistant to multiple antibiotics. In mice, gallium treatment blocked both chronic and acute infections caused by this bacterium. The study was published in the April 2, 2007, issue of the Journal of Clinical Investigation.

"The competition for iron is critical in the struggle between bacteria and host,” said senior author Pradeep Singh, M.D., Ph.D., associate professor of medicine and microbiology at the UW. "Gallium acts as a Trojan horse to iron-seeking bacteria. Because gallium looks like iron, invading bacteria are tricked, in a way, into taking it up. Unfortunately for the bacteria, gallium can't function like iron once it's inside bacterial cells.”

"We badly need new approaches to fight bacteria,” concluded Dr. Singh. "The gallium strategy isn't ready for clinical use yet. However, we think this approach is promising, and we can't afford to leave any stone unturned.”


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