Probiotic drink could help combat antibiotic resistance

A probiotic drink could become a promising new weapon in the battle against antibiotic-resistant bacteria, after scientists at the University of Birmingham engineered and patented a key genetic element that can tackle the genetic basis of resistance. The drink has potential to work against many resistant bacteria commonly found in the human gut, including E. coli, Salmonella and Klebsiella pneumoniae.

The drink works by targeting small DNA molecules, called plasmids, inside bacterial cells. These molecules frequently carry genes that give resistance to antibiotics, which the bacteria are able to use. The plasmids replicate independently, spreading between bacteria and carrying resistance genes with them.

By preventing the target plasmids from replicating, the team were able to displace the resistance genes available to the bacteria, effectively ‘re-sensitising’ them to antibiotics. Their results have been published in the journal PLOS One.

“We were able to show that if you can stop the plasmid from replicating, then most of the bacteria lose the plasmid as the bacteria grow and divide,” explained Professor Christopher Thomas, lead researcher on the project. “This means that infections that might otherwise be hard to control, even with the most powerful antibiotics available, are more likely to be treatable with standard antibiotics.”

The drink will contain bacteria (in a similar way to drinks like Yakult) carrying a new type of plasmid, which the researchers call pCURE plasmids. These work in two ways: they prevent the resistance plasmids from replicating and they also block a so-called ‘addiction system’, which the plasmids use to kill any bacteria that lose them.

In this system, the resistance plasmid carries a stable toxin and an unstable antidote into the host cell. If the plasmid is lost from the cell, the antidote breaks down, leaving the harmful toxin to attack its host. pCURE plasmids also carry the antidote, ensuring that cells that lose the resistance plasmid survive and take over the gut.

“We manipulated our pCURE plasmids to incorporate genes that block the replication of the resistance plasmid,” Prof Thomas said. “We also target the plasmid’s addiction system by designing our pCURE plasmids to ensure the antidote is still available to the host.”

The team discovered that by doubling the number of copies of the pCURE plasmid in each bacterium it became very effective at displacing different types of resistance plasmids and would spread through laboratory cultures unaided, to clear out resistance. They then collaborated with colleagues at the University of Sydney to test the pCURE plasmids in mice.

They found the pCURE plasmids worked effectively, but needed to be ‘primed’ by giving the mice an initial dose of antibiotic to reduce the number of competing bacteria. The next step is to see if plasmids can spread fast enough in human volunteers to get rid of resistance plasmids.

“This is a promising start,” Prof Thomas said. “We aim to make modifications to further improve the efficacy of our pCURE plasmids before moving towards a first clinical trial.”

Image credit: ©stock.adobe.com/au/nadisja

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