Scientists have unveiled a drug combination that destroys antibiotic-resistant germs in mice, potentially opening a new front against chronic and relapsing infections in humans.
Big Pharma had been closely interested in a compound dubbed acyldepsipeptide (ADEP), only to drop it when some germs became resistant to it.
But scientists in the United States reported on Wednesday that, when used alongside conventional antibiotics, ADEP proved to be a relentless killer.
"We decided to pair it to conventional antibiotics.... to stem the propagation of (drug) resistant cells," said study co-author Kim Lewis of Northeastern University in Boston.
The combination "completely sterilised" bacteria in a Petri dish and in mice whose thighs had been severely infected, said Lewis.
"Efficacy in an animal model is actually a pretty good predictor of efficacy in humans, so I think it is entirely realistic" that a drug may result, he added.
Humans rely on antibiotics to fight off a vast array of bacterial diseases, from tonsillitis to tuberculosis.
But antibiotics do not work for all types of bacteria, and in some types where they are effective, germs are evolving worryingly into forms that are resistant to the drug.
Some infections are caused by biofilms - slimy collections of bacterial cells that coat infected areas and block out the immune system, according to a podcast by Nature, accompanying the study in the British journal.
While antibiotics can penetrate those biofilms, they fail to clear up the infection because of so-called "persister cells".
These are hibernating cells within the biofilm that stop dividing or growing and shut down their metabolism.
The dormant cells are the main cause of chronic and relapsing bacterial infections, since conventional antibiotics can target only actively growing bacterial cells.
"We had to look for something that in a persister will activate a function, will corrupt it, force it to kill the cell," said Lewis.
The team tested ADEP in the lab and found it activates a protease in cells - protease is a protein that breaks up other proteins, eventually causing cell death.
In the experiments, the protease degraded proteins in the bacterial cells, causing these molecules to "self-digest", said Lewis.
"It doesn't matter whether that cell was growing, dormant, persister. So that compound has the ability to sterilise an infection," he said.
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