Researchers in the US have found a way to target and kill antibiotic resistant bacteria using a drug that is already approved as a treatment for bone loss.

The study was conducted by researchers at the University of North Carolina (UNC) at Chapel Hill and appears in this week’s early online edition of the Proceedings of the National Academy of Sciences .

Bacteria are in the habit of giving each other strands of DNA; this is how they pass on survival advantage, including resistance to antibiotics. An enzyme called relaxase helps them do this. Bisphosphates, which are used to treat bone loss, appear to disrupt the process and prevent the transfer of antibiotic resistance genes, and selectively cause the death of resistant bacteria.

Whenever you or I take an antibiotic, it kills the weakest bacteria in our bodies. Meanwhile the stronger ones that have developed resistance share that particular part of their DNA with others, increasing the population of bacteria that will be even harder to kill next time we take antibiotics; the bacteria in effect become stronger each time we try to kill them.

Senior author of the study, and professor of chemistry, biochemistry and biophysics at UNC-Chapel Hill, Dr Matt Redinbo said:

“Our discoveries may lead to the ability to selectively kill antibiotic-resistant bacteria in patients, and to halt the spread of resistance in clinical settings.”

Redindo and colleagues found a weakness in relaxase that helps E. coli bacteria to swap genes that confer drug resistance in lab cultures. They are now working on animal studies.

If proven to work in mammals, this could open an unexpected new door to fighting bacteria. The last decade has seen an unprecedented increase in antibiotic resistant bacteria to the point where almost every type of bacteria is now resistant, and they can cause deadly infections that are very difficult and expensive to treat.

The process by which bacteria share their DNA is known as “conjugation” and relaxase is key to its function. The description of conjugation is similar to that of worms mating. The organism opens a hole in its membrane and squirts a single strand of DNA into a neighboring organism. This process traverses a colony at lightning speed.

The researchers found that relaxase starts and stops the conjugation process. Redinbo said that:

“Relaxase is the gatekeeper, and it is also the Achilles’ heel of the resistance process.”

The scientists used x-ray crystallography to help them examine the three dimensional structure of the enzyme and find its weakness, the point at which it handles the DNA. Relaxase holds two phosphate-rich DNA strands at the same time, and the team thought perhaps they could disrupt this by plugging in a decoy using a phosphate ion from a bisphosphate compound. Redinbo’s background in cancer research provided the knowledge.

Of the available bisphosphates on the market, two did the job of blocking the site on relaxase that it uses to handle the DNA: clodronate and etidronate.

The researchers said they still don’t know how the bisphosphates kill the bacteria, but the drugs wiped out all the E. coli bacteria that carried relaxase.

“That it killed bacteria was a surprise,” said Redinbo. The drug is acting like a birth control agent, preventing antibiotic resistance from spreading.

The researchers said their results were currently only proven on E. coli so they will shortly be testing to see if bisphosphates have the same effect on other species such as Acinetobacter baumannii (hospital-acquired pneumonia), Staphylococcus aureus (staph infections) and Burkholderia (lung infections).

Speculating on applications of their discovery should it prove to be successful on other bacteria, Redinbo said he could see it working where clinicians can control the dosage such as on skin and in the digestive tract. Other uses could include disinfectants and treatments for farm animals he said.

The researchers have formed a small company to exploit the technology and have filed a patent for their discovery.

Click here for Proceedings of the National Academy of Sciences.

Click here for UNC-Chapel Hill.

Written by: Catharine Paddock
Writer: Medical News Today