Stealth drug fights resistant bacteria

Rather than looking for drugs that break into bacteria, researchers have tried a new approach: to encourage bacteria to take a molecule that looks like food, but wreaks havoc once inside. A study of this approach shows initial success in mice and humans.

The work is described in the September 26, 2018 issue of Translational medicine of sciences. The two principal investigators, Pradeep Singh and Christopher Goss, are faculty members at the University of Washington (UW) School of Medicine.

Their study focused on a superbug, Pseudomonas aeruginosa, which causes infection in the lungs, urinary tract, wounds and elsewhere. This is a particular problem in patients whose ability to fight infection is impaired due to diseases such as cystic fibrosis, cancer and AIDS.

The researchers studied gallium because it is a metal similar to iron, a nutrient essential for bacteria during an infection.

"The body makes great efforts to keep iron away from bacteria, and infectious organisms generate special systems for importing iron and stealing it at the host," said Singh, lead author and professor of microbiology and microbiology. medicine.

<a rel = "lightbox" href = "https://3c1703fe8d.site.internapcdn.net/newman/gfx/news/2018/1-hitemwhereth.jpg" title = "Colonies of Pseudomonas bacteria growing on an agar plate. Credit: Singh Lab, University of Washington ">

Goss, professor of medicine and pediatrics UW and first author of the newspaper, described gallium as a Trojan horse. "Gallium not only fails to feed bacteria like iron does, it hurts them".

The researchers also discovered how gallium works. "Gallium disrupts the machinery used by bacteria to make a new DNA, and without it the bacteria can not multiply," said co-author Bradley Britigan, professor of internal medicine at the University Medical Center. from Nebraska. "This process and other essential processes require iron, and gallium is a monkey key that stops the system."

In laboratory studies, the bacteria developed gallium resistance at low levels and gallium potency was increased in association with some existing antibiotics. These factors led researchers to test gallium in mice and then in humans.

In mice, researchers found that a single dose cured deadly lung infections. They then studied gallium in 20 people with cystic fibrosis and difficult-to-treat lung infections caused by antibiotic resistance. Pseudomonas bacteria.

<a rel = "lightbox" href = "https://3c1703fe8d.site.internapcdn.net/newman/gfx/news/2018/2-hitemwhereth.jpg" title = "In this radiographic image, Pseudomonas The infection in a lung is more visible at the top of the organ, which appears in the form of a torn shroud above the cavities. Credit: Singh Lab, University of Washington ">

"Our preliminary study of a small group of people with CF suggests that gallium is safe and improves the lung function of patients," Goss said. "These are exciting results, but we need to do more studies to determine if gallium can be turned into a safe routine treatment."

The idea of ​​disrupting bacterial nutrition as an antimicrobial strategy was raised in the 1800s by Louis Pasteur, but these treatments were difficult to develop.

Could gallium therapies be an exception to this experience? "It is our hope, and we are encouraged by these results, but we must be cautious and do more work before we know," Singh said.

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More information:
C.H. Goss el al., "Gallium disrupts the bacterial metabolism of iron and has therapeutic effects in mice and humans suffering from pulmonary infections" Translational medicine of sciences (2018). stm.sciencemag.org/lookup/doi/… scitranslmed.aat7520