Gallium Trojan horse strategy defeats drug-resistant bacteria

An article in the Journal of Clinical Investigation outlines how a new antimicrobial approach kills bacteria in laboratory experiments and eliminate life-threatening infections in mice by interfering with a key bacterial nutrient. Iron is critical for the growth of bacteria and for their ability to form biofilms, slime-encased colonies of microbes that cause many chronic infections. "Gallium acts as a Trojan horse to iron-seeking bacteria," said Pradeep Singh (senior author). "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."

The work is by by workers from the University of Iowa and the University of Cincinnati. Rather than trying to find agents that best killed bacteria in test tubes, the researchers sought to intensify the stress imposed on microbes by one of the body's own defense mechanisms. The study's senior author Singh explained "The competition for iron is critical in the struggle between bacteria and host. The body has potent defense mechanisms to keep iron away from infecting organisms, and invaders must steal some if they are to survive."

"Because iron is so important in infection, we thought infecting bacteria might be vulnerable to interventions that target iron," explained Yukihiro Kaneko, senior fellow in microbiology at the UW and the study's lead author. To accomplish this, the researchers used gallium, a metal related in some ways to iron.

The researchers showed that gallium killed microbes, and prevented the formation of biofilms. Importantly, gallium's action was intensified in low iron condition, like those that exist in the human body. Gallium was even effective against strains of Pseudomonas aeruginosa from cystic fibrosis patients that were resistant to multiple antibiotics. In mice, gallium treatment blocked both chronic and acute infections caused by this bacterium. The idea of using gallium as a substitute for iron was developed by a group led by Bradley Britigan, a researcher at the University of Cincinnati and a co-author on this study.

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