Modified antibiotic can fight drug resistant bacteria

Scientists have re-engineered a lifesaving antibiotic, one of the most-used antibiotics in the world, in a move that could eliminate the threat of antibiotic-resistant infections.

The antibiotic called vancomycin is used to treat a number of bacterial infections. But in a world that is desperately running out of defenses against bacterial diseases, modification of the antibiotic called vancomycin is designed to be ultra-tough and appears to be a thousand times more potent than the old version of the drug, a study published in the scientific journal Proceedings of the National Academy of Sciences (PNAS) reports.

The team of US researchers 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,” the scientists said while announcing the findings last week.

One hard-to-treat infection that has been worrying doctors is vancomycin-resistant enterococci also known as VRE. For 60 years, vancomycin has been saving lives, widely prescribed for staph infections (types of germs commonly found on the skin or in the nose of even healthy individuals) and diarrhoea, among other potential killers. However, resistance begun to be reported as early as 1987.

Today, bacteria resistant to it is appearing widely, but lead researcher Professor Dale Boger of The Scripps Research Institute (TSRI) an independent, not-for-profit organisation focusing on research in the biomedical sciences, described it as “magical” for the time it has lasted, indicating that its disruption of bacterial cell wall maturation is particularly hard to overcome.

While other researchers have been chasing new antibiotics, Boger sought to breathe new life into vancomycin, making it capable of fighting bacteria in three different ways and much less likely to be dodged by bacteria.

WORK-AROUND MECHANISM

“With these modifications, you need less of the drug to have the same effect,” Boger said in a statement.

The new study shows that scientists can make a third modification—which in a new way interferes with a bacterium’s cell wall—with promising results. For instance, combined with the 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.

Previous studies by the team showed it was possible to add two modifications to vancomycin, a drug they labelled “magical” because of its strength against infection, to make it even more potent and reduce the amount of the medicine needed to have the same effect.

Early this year, the World Health Organisation warned that antibiotic resistance is one of the biggest threats to global health. The WHO notes that antibiotics previously potent in dealing with a host of common diseases and infections are fast losing their effectiveness.

The discovery makes this version of vancomycin the first antibiotic to have three independent mechanisms of action. “This increases the durability of this antibiotic,” said Boger.

“Organisms just cannot 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.”

In a laboratory, the modified drug was able to kill samples of VRE and retained nearly full potency after 50 rounds of exposure to the bacterium. Small doses of the new drug were also shown to kill non-resistant enterococci bacteria, along with VRE.

Dale Boger explained: “We made one change to the molecule vancomycin that overcomes what is the present resistance to vancomycin, and then we added to the molecule, two small changes that built into the molecule, two additional ways in which it can kill bacteria.

So the antibiotic has three different, we call them ‘mechanisms’, by which it kills bacteria. And resistance to such an antibiotic would be very difficult to emerge. So it is a molecule designed specifically to address the emergence of resistance.”

The modified antibiotic is however yet to be tested in animals and people. Currently, it takes 30 steps to synthesize the modified product with all three tweaks included, making it prohibitively expensive for widespread use. The next step in this research therefore is to design a way to synthesize the new drug using fewer steps. Prof Nigel Brown of the Microbiology Society said: “This development could be hugely important.

“Vancomycin is an antibiotic of last resort against some serious infections. There has been great concern that resistance has been emerging.”

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The promise

In a laboratory, the modified drug was able to kill samples of vancomycin-resistant enterococci also known as VRE and retained nearly full potency after 50 rounds of exposure to the bacterium. Small doses of the new drug were also shown to kill non-resistant enterococci bacteria, along with VRE