Antibiotic resistance could leave humanity returning to an age when simple infections were fatal and surgery was life threatening, the World Health Organisation says.
'Superbugs', resistant to antibiotics, cause 700,000 deaths a year, a number expected to rise much further in the years to come.
Before antibiotics were invented, 40 percent of people used to die of infections.
The problem is we are not adding to our armoury – very few antibiotics have been brought to market in the last 30 years.
So a research team from the University of Queensland decided to find a way to tackle the problem. And rather than looking at new drugs, they looked at existing ones.
They developed a method of supercharging an old drug to make a meaner antibiotic, capable of taking on the superbugs.
The team was led by Dr Mark Blaskovich, who says the research could revitalise other drugs.
He says the problem is not new.
“Every single antibiotic introduced into human use, generally within a couple of years, sometimes longer, resistance has been detected.
“But in the past we were able to develop new antibiotics fast enough to stay ahead of the bacteria developing resistance.”
Big pharma isn’t making them he says, and for sound economic reasons.
It costs the same for a pharmaceutical to bring an antibiotic to market as it does a cholesterol-lowering or anti-cancer drug.
“With a cholesterol-lowering drug you have many, many patients that have to take it for the rest of their lives, as it’s treating a condition not curing it.
“For an anti-cancer drug, the market can charge $100,000 per treatment.”
By comparison an antibiotic sells for pennies and is used for a short period of time.
“You take a two-week course and you’re cured, you don’t have the disease or infection anymore.”
With so many generic antibiotics available that often will do the job, the market won’t allow for an antibiotic with a premium attached.
“For some reason they are incredibly undervalued.”
Blaskovich and his team have been looking at revamping a drug first introduced in the 1950s.
Vancomycin was found in the 1970s to be effective against golden staph infections - one of the few antibiotics that were - but gradually its efficacy has waned.
Vancomycin works by targeting the cell wall structure which surrounds the bacteria and keeps it intact. The drug stops the cell wall from growing, causing the bacteria to eventually rupture.
There are a number of different mechanisms by which bacteria can become resistant to vancomycin, Blaskovich says.
One is they grow a lot more of the cell wall so it’s harder for the drug to reach its target. Another is to mutate the target so the drug binds to it less strongly.
So how did Blaskovich and his team supercharge the drug?
The target to which vancomycin binds is embedded in the liquid membrane that surrounds the outer side of the bacteria, like “a plastic bag enclosing what’s inside,” Blaskovich says.
“Our idea was if we take vancomycin and chemically modify it and add some other substituents which allow it to target specifically to the type of membrane found in a bacteria, that gives us a potential additional binding mechanism as well as binding to the cell walls.”
This gives the drug two potential binding sites and so increases its potency, he says.
Also the outer wall of a bacteria has a negative charge so the researchers gave vancomycin a further tweak.
“If we put a positive charge on vancomycin we can selectively target the membranes on bacterial cells in preference to the membranes on human cells.”
This improves the drug’s selectivity and decreases its toxicity.
He says this kind of pharmaceutical retrofitting could be used for other classes of drugs, but warns it’s not a quick process.
It takes five to 10 years to demonstrate that a drug is safe and works on humans.
“It’s this lag time between doing the basic research and when an antibiotic will be approved to be used on humans that’s a real concern. Because if we’re not investing now by the time the highly resistant strains evolve in the next ten years it’ll be too late to develop new antibiotics.”