The lack of new antibiotics is among the most critical challenges facing medicine. Researchers have been on the hunt for new drugs to combat “superbugs” that cannot be penetrated by current antibiotics.
Rather than looking for drugs that forcibly penetrate bacteria, researchers tried a new approach: tricking bacteria into taking up a molecule that looks like food, but wreaks havoc once inside. A study of this approach shows initial success in mice and humans.
Bradley Britigan, M.D., dean of the UNMC College of Medicine and professor of internal medicine at UNMC, is a co-author of the study. The work is described in the Sept. 26 issue of Science Translational Medicine. The two primary investigators, Pradeep Singh, M.D., and Christopher Goss, M.D, are faculty members at the University of Washington School of Medicine.
The study focused on superbug, Pseudomonas aeruginosa, which causes infection in the lungs, urinary tract, wounds and elsewhere. It is a particular problem in patients whose ability to fight infection is impaired because of illnesses such as cystic fibrosis, cancer and AIDS.
The researchers studied gallium because it is a metal similar to iron, a critical nutrient for bacteria during infection. The researchers also discovered how gallium works.
“Gallium disrupts machinery that bacteria use to make new DNA, and without this the bacteria can’t multiply,” Dr. Britigan said. “This and other essential processes require iron, and gallium is a monkey wrench that shuts the system down.”
Dr. Singh, senior author, said the body goes to great lengths to keep iron away from bacteria. “And infecting organisms crank up special systems to import iron and steal it from the host.”
Dr. Goss described gallium as a Trojan horse. “Gallium not only fails to nourish bacteria as iron would, it actually harms them.”
In lab studies, bacteria developed resistance to gallium at low rates, and gallium’s potency was increased when used in combination with some existing antibiotics. These factors led the researchers to test gallium in mice and then in humans.
In mice, researchers found that a single dose cured lethal lung infections. They then studied gallium in 20 people with cystic fibrosis (CF) and difficult-to-treat lung infections caused by antibiotic-resistant Pseudomonas bacteria.
“Our preliminary study in a small group of people with CF suggests that gallium is safe and improves patients’ lung function,” Dr. Goss said. “These are exciting results, but we need to do more studies to determine if gallium can be developed into a routine, safe treatment.”