Scientists develop molecule that attacks natural defences of superbugs

Anne Gulland

Scientists have developed a molecule that can penetrate the natural defences of superbugs, giving a new lease of life to a “last-resort” antibiotic. 

The molecule, created by researchers in Ireland and Spain, was given in conjunction with the antibiotic colistin, rendering it 16 times more effective than if it had been administered on its own.

Antimicrobial resistance (AMR) is an increasing global threat, with a recent report from the United Nations warning that if left unchecked it could kill 10 million people by 2050.

Resistance is bacteria’s natural defence to the threat posed by antibiotics but alternatives to existing treatments are in desperately short supply - so adding new elements to an already commonly-used antibiotic is a promising step forward.

The study, published in the journal Future Medicinal Chemistry, shows how a combination of the drug and the molecule interferes with bacteria's natural communication system.

When some bacteria are under attack from an antibiotic they produce a signal which alerts them to the incoming danger. They then produce a biofilm that acts as a shield, stopping the antibiotic getting to the bacteria.

The new molecule overrides this system so the bacteria do not receive a signal to produce a biofilm - enabling the antibiotic to treat the infection.

The researchers added the molecule to the drug colistin and looked at the effect on families of drug-resistant bacteria that infect the lung and are commonly found in patients with cystic fibrosis.

Dr Tim O’Sullivan, lecturer in pharmaceutical chemistry at University College Cork and one of the authors of the paper, said colistin is what is known as a “last resort” antibiotic, meaning it can only be used when other drugs have failed.

“When used at normal levels colistin is potentially toxic but we have shown that when used in conjunction with our compound you can reduce the amount of antibiotic required by about 16 times,” he said.

This is a “proof of concept” study and has yet to be tested in humans. The next step is to determine whether other bacteria could be targeted by the compound. 

“What’s unique about our study is that all bacteria have a communication system and different families of bacteria have different languages. The communication system we looked at is much less well studied than others,” said Dr O'Sullivan. 

He added: “As more microbes develop resistance to current antibiotics, and relatively few new antibiotics are coming to market, we need to identify new ways of dealing with resistant infections. The approach outlined in our work has significant potential."

Dr Pol Huedo, co-author of the study, said the findings “validate the strategy of interfering with bacterial communication to combat difficult-to-treat infections caused by resistant organisms".

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