We’re currently in dire need of new weapons against infectious bacteria, especially those in a tough-to-kill class known as gram-negative bacteria. Now, researchers at Northeastern University have discovered just that, hiding in the gut of a tiny, soil-dwelling, parasitic worm. Tests on mice have so far proved promising.
For decades we’ve had the upper hand over bacteria, clearing out many infections fairly easily with antibiotics. But extensive use has led to an arms race between us and bacteria. As they evolve resistance to our best drugs, we develop new ones and use those until the bugs become resistant to those too.
But this cycle is starting to break down, and not in our favor. Developing new drugs is time and cost-intensive process, and bacteria are evolving resistances faster than we can keep up. There are now “superbugs” that are resistant to all known drugs. The situation is getting so bad that a recent report warned that superbugs could kill up to 10 million people a year by 2050, casting us back into the “dark ages of medicine.”
“We are running out of antibiotics,” says Kim Lewis, director of Northeastern’s Antimicrobial Discovery Center (ADC) and lead researcher on the new study. “We need to be looking for novel compounds with no pre-existing resistance in the clinic or the population.”
Luckily, humans aren’t the only organisms looking to kill bacteria – other bacteria are always out for new weapons to kill off competitors for food. So rather than develop drugs from scratch, one promising avenue is to find these microscopic weapons of war and adapt them for our own use.
And now, a team from the ADC has done just that. The new antibiotic, dubbed darobactin, was discovered in the gut microbiome of nematodes. These tiny worms are parasites that live inside the digestive systems of caterpillars and other insects. Once there, they release a bacteria called Photorhabdus, which kill the caterpillar so that both the worm and bacteria can feast on it.
And in order to prevent other opportunistic microbes from stealing the meal, the Photorhabdus produce an antibiotic compound. And this was the basis for darobactin.
Importantly, the new compound can kill gram-negative bacteria, a notoriously hardy class of bugs that have a second membrane in their cell walls. The researchers found that darobactin binds to a protein called BamA, jamming the mechanism that the bug uses to build its cell wall and killing them.
The researchers tested the drug against gram-negative bacteria both in the lab and in mice, and found it to be effective. And while there’s always the chance that bacteria will eventually develop resistances to any new drugs, the team noticed an interesting twist. Bugs that evolved resistance to darobactin lost the ability to infect mice. The BamA protein appears to be too important for the bacteria to change, and hopefully that should mean the drug remains unresisted for longer.
The team has previously found another antibiotic candidate in soil bacteria. In 2015, Lewis’s lab discovered teixobactin, which targets gram-positive bacteria.
Of course, as promising as results in mice and lab dishes may seem, they may not carry across to humans. But the team holds out hope for these next steps.
The research was published in the journal Nature.
Source: Northeastern University