Oxford scientists cancel "genetic catalyst" that helps bacteria evolve drug resistance
Humanity might not go out with a bang, but a sniffle – at least if the terrifyingly-plausible "superbug" scenario comes to pass. As bacteria increasingly evolve resistance to antibiotics, we could be cast back into "the dark ages of medicine" in the next few decades. But now we might have a new way to fight back. Researchers at Oxford University have discovered a "genetic catalyst" that lets the bugs develop resistance – and they might be able to switch it off.
Thanks to the overprescription and overuse of antibiotics, bacteria are fast developing tolerances to them. As more and more drugs begin to fail – including our last line of defense – we could be headed for a future where the risk of infection makes even the most basic of injuries or surgical procedures life-threatening again.
Luckily, scientists around the world are working to restock our arsenal against superbugs. Along with developing new antibiotics and supercharging old ones, researchers are experimenting with new polymers, gels, lights, materials, molecules, skin patches, and even ways to pit pathogens against each other.
But the Oxford team decided to take the fight to the bacteria themselves, with the hope of eventually disarming the ability to develop resistance. To do so, they studied how different bacteria evolve resistance at different rates, and set out to find the specific genes responsible. The researchers exposed different species of Pseudomonas bacteria to the common antibiotic ceftazidime, and found that one particular gene seems to be the culprit.
"We identified that the presence of a gene known as ampR is a major cause of this variation," says Craig MacLean, senior author of the study. "ampR is a master regulatory gene that switches the expression of hundreds of other genes on and off, including genes involved in antibiotic resistance. This gene acts as an evolutionary catalyst for antibiotic resistance. Put simply, species that carry the ampR gene evolve resistance at a higher rate than species that lack this gene. ampR has this effect because it makes it easier for random mutations to increase the expression of antibiotic resistance genes."
To test their find, the researchers turned to an enzyme inhibitor called avibactam, which is known to block a key resistance gene that ampR controls. The team combined avibactam and ceftazidime, then exposed cultures of Pseudomonas aeruginosa to the mix. This bacteria carries the ampR gene and has been shown to evolve resistance to ceftazidime quite quickly, but adding avibactam managed to wipe out the bugs "spectacularly well" before they could evolve resistance.
By removing the evolutionary advantage of the ampR gene, the team says that the new technique kills bacteria without driving the spread of resistance. While the discovery is promising, the researchers say that follow-up studies should be conducted in the body to make sure it works in that context.
The research was published in the journal Nature Ecology & Evolution.
Source: Oxford University