Scientists in the United States have succeeded in modifying a lifesaving antibiotic called vancomycin to make it more powerful; an advance they predict will reduce the threat of antibiotic-resistant infections for years to come.
Vancomycin has been prescribed by doctors for 60 years, but bacteria are only now becoming resistant to it. It has been one of the main tools used against infections caused by bacteria known as enterococci; MRSA and Clostridium difficile – they are among a class of superbugs resistant to antibiotics.
These microbes are among the biggest cause of hospital-acquired infections across the globe, notably vancomycin-resistant enterococci (VRE), and cause particular difficulties for people whose immune system is suppressed.
The World Health Organisation warns antibiotic resistance is one of the biggest threats to global health, with major diseases becoming harder to treat because the drugs used on them are becoming less effective.
Researchers at the Scripps Research Institute (TSRI) in La Jolla, California, led by Dr Dale Boger, discovered a way to structurally modify vancomycin to make an already-powerful version of the antibiotic even more potent. "Doctors could use this modified form of vancomycin without fear of resistance emerging," he predicted.
Because this antibiotic has been so effective up to recently, it suggests bacteria already have a hard time overcoming its original "mechanism of action", which works by disrupting how bacteria form cell walls, explained Dr Boger. His team's findings are published today in the journal Proceedings of the National Academy of Sciences.
‘Magical’
He said vancomycin was “magical” because of its proven strength against infections. Previous studies by his team at TSRI had shown it was possible to add two modifications to vancomycin to make it even more potent. “With these modifications, you need less of the drug to have the same effect,” Dr Boger said.
The new study shows scientists can make a third modification which interferes with a bacterium’s cell wall. “Combined with previous modifications, this alteration gives vancomycin a 1,000-fold increase in activity, meaning doctors would need to use less of the antibiotic to fight infection,” according to TSRI.
The discovery makes this version of vancomycin the first antibiotic to have three independent mechanisms of action. “This increases the durability of this antibiotic,” Dr Boger said. “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”
Tested against Enterococci bacteria, the new version of vancomycin killed both VRE and original forms of enterococci. The next step was to design a way to synthesise the modified vancomycin using fewer steps in the lab, as the current method takes 30 steps. But Dr Boger said this was the “easy part” of the project, compared with the challenge of designing the molecule in the first place.
Prof Colum Dunne, director of research at University of Limerick Medical School, said the research had particular relevance to Ireland, as the Republic has the highest reported rate in Europe of VRE, based on recorded bloodstream infections – the resistant form of the disease is approaching 50 per cent of cases.
Real benefits
He said the new form of vancomycin, if developed by a pharmaceutical company, would bring real benefits to patients, provided it was used as a “last resort” product. It should be held in reserve as “the best weapon you have,” he added.
He cautioned against belief it could be a silver bullet, as in his view it would be inevitable that resistance to vancomycin’s new version would build up, due to factors such as reduced vigilance as a consequence of false confidence, and the ways antibiotics would be administered as a consequence.
The process of modifying an antibiotic was not unusual, Prof Dunne said, as it was often done to extend product shelf-life. The antibiotic pipeline for a lot of companies and research “discovery programmes” was not as rich as it used to be but the process could improve drug efficacy and reduce side effects.
