Page last updated at 03:24 GMT, Friday, 4 December 2009

'Double trouble' antibiotic hope

Antibiotic
Antibiotic resistance is an increasing problem

A "double-headed" antibiotic could lead to powerful new drugs to beat resistance, say UK researchers.

It sticks to bacteria in two places making it more potent and reducing the chance that bacteria will adapt to resist it, the journal Science reports.

Although not itself suitable for use in patients, it is hoped drugs can be created based on the same principle.

But the news comes as experts warn that excessive regulation is preventing new antibiotics being developed.

An editorial in The Lancet medical journal has called for greater efforts to develop new antibiotics.

A recent EU report found that only 15 antibacterial drugs that offer a potential benefit over existing drugs are in development, and only five have reached the final stage of the trials process.

And the British Society for Antimicrobial Chemotherapy has set up a working group to try and address some of the barriers.

Natural compound

In the latest study, researchers looked at a naturally occurring molecule made by soil bacteria called simocyclinone.

It attacks an enzyme in bacteria called DNA gyrase, stopping them from growing.

This enzyme is also targeted by a commonly used group of antibiotics called fluoroquinolones, but resistance to these drugs is growing.

The team showed that simocyclinone binds to a completely different, previously unexploited part of the enzyme and also latches on in two places or "pockets".

The "double-headed" nature of the antibiotic makes it 100 times more powerful than if each "head" attached to the bacteria individually.

You could say that this is a case of two heads being better than one
Professor Tony Maxwell, study leader

And because bacteria would have to mutate in both binding sites, it cuts the potential for resistance.

Simocyclinone is a fairly large molecule and can not easily get into bacterial cells.

By designing molecules which bind to the enzyme in the same way, researchers say more effective antibiotics could be developed.

Drug design

Study leader Professor Tony Maxwell from the John Innes Centre in Norwich, said: "If you can knock out this enzyme, you have a potential new drug," said Professor Maxwell.

"The fact that there are two pockets means that it might require simultaneous mutations in both pockets for the bacteria to acquire full resistance to the drug, which is much less likely.

"You could say that this is a case of two heads being better than one."

Professor Laura Piddock from the British Society for Antimicrobial Chemotherapy, said there are huge hurdles to developing antibiotics.

"Antibiotic drug development worldwide is in the doldrums because it's very expensive to get drugs through the regulatory process.

"These results are exciting because having a single molecule that targets two separate parts of the enzyme is new and novel.

"But clearly if someone comes up with a useable version of this molecule they're going to have to overcome some hurdles, which are so profound it makes you very pessimistic."



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