image: Gallium synergized with the antibiotic colistin (Col) in killing P. aeruginosa bacteria in plate cultures. This material relates to a paper that appeared in the Sept. 26, 2018, issue of Science Translational Medicine, published by AAAS. The paper, by C.H. Goss at University of Washington School of Medicine in Seattle, Wash.; and colleagues was titled, "Gallium disrupts bacterial iron metabolism and has therapeutic effects in mice and humans with lung infections." view more
Credit: C.H. Goss <i>et al., Science Translational Medicine </i>(2018)]
A new antibiotic treatment that contains the heavy metal gallium safely combated bacterial growth in mice and showed signs of efficacy in a preliminary phase 1 clinical trial of patients with cystic fibrosis or chronic lung infections. The findings support the idea that disrupting bacterial metabolism with gallium and other metals could be a viable alternative to standard antibiotics. Before the invention of antibiotics, metals such as copper and mercury were commonly used as antimicrobials because of their known toxicity against many bacterial species. Prompted by the growing specter of antibiotic resistance, Christopher Goss and colleagues repurposed gallium - an elemental metal used in alloys and semiconductors - as an antimicrobial against lung infection-causing bacteria. Their treatment takes advantage of the fact that gallium is structurally similar to iron (which is critical for bacterial nutrition and metabolism), allowing the metal to act as a "Trojan horse" and sneak into the bacterium's metabolic system. The authors showed that small concentrations of gallium curtailed bacterial growth in sputum samples from patients infected with Pseudomonas aeruginosa, a species that often infects hospital patients. They noted that resistance to gallium developed slowly, and the metal was effective when paired with existing antibiotics such as colistin and tobramycin. The team then found that intravenous gallium administration reduced bacterial counts and improved survival in a mouse model of P. aeruginosa infection. A proof-of-principle clinical trial showed that 28 days of intravenous gallium treatment improved lung function in 20 patients with either cystic fibrosis or chronic P. aeruginosa lung infections without causing serious adverse effects. The authors plan to conduct larger clinical trials to further determine gallium's safety, therapeutic efficacy and effectiveness in conjunction with established antibiotics.
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Journal
Science Translational Medicine