Researchers have derived an antibiotic from microbes living in the sandy soil of North Carolina. Because it works completely differently than others before it, clovibactin might help turn the tide in the battle against superbugs that resist current drugs.
In developing the antibiotic, researchers from Germany and the United States made use of a device known as iCHip that allows scientists to culture bacteria that up till now were considered "bacterial dark matter," or bacteria that simply can't be grown in a lab. Interestingly, 99% of all bacteria fall into this category. iCHip was developed by a small start-up known as NovoBiotic Pharmaceuticals and microbiologist Kim Lewis from Northeastern University in Boston.
This time around, the device helped researchers find clovibactin, an antibiotic that is produced by soil microbes found in North Carolina known as Eleftheria terrae subspecies carolina. These bacteria produce the clovibactin to attack, and therefore help them outcompete, other soil microbes.
"Clovibactin is different," said study co-author Markus Weingarth, a researcher from the Chemistry Department of Utrecht University. "Since Clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance."
Cagey strategy
Once the antibiotic was discovered, the researchers went to work figuring out just how it worked. They discovered that its killing mechanism is different from that of current antibiotics. It basically forms a cage around three different precursor molecules that bacterial invaders use to build their cell walls. In fact, the name "clovibactin" comes from "klovi," the Greek word for cage because of its novel method of action.
While some current antibiotics also work by destroying bacterial cell walls, clovibactin is unique in the way it locks up these molecules known as pyrophosphates.
"Clovibactin wraps around the pyrophosphate like a tightly sitting glove," said Weingarth. "Like a cage that encloses its target. As Clovibactin only binds to the immutable, conserved part of its targets, bacteria will have a much harder time developing any resistance against it. In fact, we did not observe any resistance to Clovibactin in our studies."
Bolstering the hope that clovibactin can penetrate the defenses of antibiotic-resistant superbugs is that fact that it goes a few steps further in its fight against bacteria.
Suicide trigger
When the antibiotic attaches itself to harmful bacteria, it sends out filaments that further bind and destroy the bug. It also causes the bacteria to release enzymes known as autolysins that further help them commit suicide by dissolve their own cell walls.
"The multi-target attack mechanism of clovibactin blocks bacterial cell wall synthesis simultaneously at different positions," said study co-author Tanja Schneider from the University of Bonn in Germany. "This improves the drug’s activity and substantially increases its robustness to resistance development."
In mouse studies, the clovibactin was effective in fighting a wide range of pathogens and seemed particularly successful against gram-positive bacteria such as those that cause common hospital infections including MRSA, staph, and strep as well as other invaders that cause a range of diseases including tuberculosis.
The research team now plans to figure out how to capitalize on the effectiveness of clovibactin and says it will take some time before the antibiotic is widely available as medication, as it will have to go down the usual pathway of clinical trials and approvals.
The study has been published in the journal, Cell.
Sources: University of Bonn, Utrecht University
