All over the world, antibiotics are failing at fighting off infectious bacteria more and more every day. The hardest to kill class is called gram-negative bacteria – and they are getting really good at becoming resistant to our drugs. To find a solution to this situation, researchers are persistently looking for new weapons against the bacteria, and a team from Northeastern University has found one in the ground – in the gut of a tiny parasitic worm to be precise. The researchers tested it on mice and achieved promising results!
At the beginning of our war against bacteria, with the weapon of antibiotics freshly at hand, we had the upper hand clearing out many infections quickly. However, as time passed and we overused the medicines, the bacteria started to learn the way of the weapon and were able to trump it. We started losing some battles in the war. The bacteria were evolving faster than ever, becoming resistant to our best drugs. Shortly after we develop new ones, they’d find a way to become resistant to those too.
It’s starting to look as if we could lose the upper hand. It costs a lot of money and takes a lot of time to develop new drugs. The bacteria are evolving resistances quicker than we can make new antibiotics. Now, there are “superbugs” resistant to all known drugs! A recent report writes that by 2050, superbugs could kill up to 10 million people a year, ultimately casting us back into the “dark ages of medicine.”
Kim Lewis, the lead researcher on the new study and director of Northeastern’s Antimicrobial Discovery Center (ADC), said:
We are running out of antibiotics. We need to be looking for novel compounds with no pre-existing resistance in the clinic or the population.
This is why the team from ADC started looking in new places for new material to make antibiotics in a way that has never been done before. Seeing as humans aren’t the only organisms looking to kill bacteria, the researchers looked for other organisms that are – specifically, other bacteria that are. Bacteria have to have weapons to kill off other bacteria because they are competitors for food!
The team realized that by finding how other bacteria kill off their competition, they could use their microscopic weapons and adapt them for human use. As a bonus, they could develop drugs quicker because they don’t have to make them from scratch this way! From this brilliant idea, a new antibiotic was born – called darobactin – and it was found in the gut microbiome of nematodes.
Nematodes are parasites that live inside the digestive systems of caterpillars and sometimes other insects. They kill the caterpillar from the inside by releasing a bacterium called Photorhabdus. When the insect dies, the nematode and its bacteria can feast on their host. Meanwhile, the Photorhabdus produces an antibiotic compound to prevent other opportunistic microbes from stealing the meal. That compound was the basis for darobactin.
The gram-negative bacteria are the hardest to kill because they have a second membrane in their cell walls. The newly discovered compound can kill gram-negative bacteria! In experiments, the researchers found that darobactin binds to a protein called BamA. When it does, it jams the mechanism that the gram-negative bacteria use to build its cell wall, so it dies.
The drug was tested in the lab and on mice. The drug was effective at killing gram-negative bacteria. What was most exciting even was that the bugs that evolved resistance to darobactin lost their ability to infect mice. It appears that the BamA protein is far too essential for the bacteria to alter. The team hopes this means the drug will remain unresisted for a long time.
The next phase of the study is to see if the results are the same in humans. The research has been published in the journal Nature.
