Since the discovery of penicillin began the antibiotic revolution in 1928, we have lived in a golden age of relative safety from infection. But the bacteria are catching up: they are able to develop resistance to antibiotic drugs quicker than we are able to invent new medicines. The rise of drug-resistant bacteria is one of the greatest threats to public health in the 21st century, according to the World Health Organisation.
The tide might finally be turning, however, with the development of a new triple-threat drug that aims to outsmart bacterial evolution.
Publishing this week in the Proceedings of the National Academy of Sciences, scientists at the Scripps Research Institute in the US report a new, synthetic version of a classic antibiotic that fights bacteria in three separate ways.
Most new antibiotic drugs start to lose their effectiveness just a few years after release into the marketplace. For example, penicillin resistance was observed even before the drug was released as a therapeutic.
However, one drug that has proven itself over time is vancomycin. Itself produced by a non-hazardous soil bacteria, it is lethal against most of the bacteria that invade mammals. It has been widely used since the 1950s, and has only recently begun to lose its potency.
Vancomycin is so hard for bacteria to overcome because it attacks the building blocks used to synthesise the bacterial cell wall. Bacteria have a difficult time finding ways to counter this, as the cell wall is a central part of their defence.
The team at Scripps, led by Dale Boger, made synthetic versions of vancomycin that included two additional ways to destabilise the cell wall. This is the first time that a triple-acting antibiotic has been reported. By combining the three approaches, the new antibiotic showed more than 1,000 times the activity against common drug-resistant bacteria.
“With these modifications, you need less of the drug to have the same effect,” Boger said.
Even more importantly, the new triple-acting drug is expected to be highly resilient in the clinic, perhaps offering even longer than the 60 years the original vancomycin has evaded resistance. It is thought that even if a bacterium can overcome one of the drug’s effects, it should be killed by the other two modes of action, meaning that the ability to overcome the first effect won’t be passed to future generations.
Boger’s new antibiotic is chemically complex, making it hard to produce on large scale, which might hinder efforts to bring it to the public. However, Boger says, “Making this molecule is important, even by the current approach, if the failure of antibiotics continues.”