Gram-negative bacteria, such as E. coli, are found everywhere and many cause disease. Unfortunately, unlike Gram-positive bacteria, they are surrounded by a barrier called the outer membrane that protected the bacteria from antibiotic treatment. Few of the currently available antibiotics can penetrate this barrier and new antibiotics are urgently needed to combat Gram-negative bacteria infection. 

Researchers at Northeastern University investigated bacteria that lives in the gut of a parasitic worm. The researchers reasoned that worm gut bacteria need to produce antibiotics to fend themselves and these antibiotics must be non-toxic to the worm host. They found that a bacteria Photorhabdus khanii produces an antibiotic called darobactin that can kill E. coli and other Gram-negative bacteria but not Gram-positive bacteria. Darobactin does not penetrate the outer membrane barrier. Instead, it disrupts BamA, an important protein located on the barrier that is critical for maintaining the outer membrane barrier.  Darobactin was found to be effective at treating mice infected with Gram-negative bacteria and non-toxic to human cells.

This study reveals a new antibiotic that kills drug-resistant bacteria in a totally new way. If successfully developed into a drug that is safe and potent, darobactin may save over ten thousand lives per year in the US alone. Darobactin might also be used together with the currently available antibiotics that cannot penetrate the barrier since darobactin interfere with the barrier integrity, making old drugs useful again.

Managing Correspondent: Veerasak (Jeep) Srisuknimit

Original Paper: Nature

Press article: News@Northeastern, Science Alert

Related SITN articles: Less of the Same: Rebooting the antibiotic pipeline, Have antibiotic resistant bacteria met their match? A new method for antibiotic discovery that could change the arms race.

Image Credit: Jonathan D. Eisenback, Virginia Polytechnic Institute and State University, Bugwood.org