The researchers suggest many drugs already approved by the FDA for other purposes have antibiotic potential, and, because they have multiple targets, it would be harder for bacteria to become resistant to them.
This was the conclusion of a study by a team of chemists from the University of Illinois at Urbana-Champaign, who report their findings in the Proceedings of the National Academy of Sciences.
The team also suggests that because the drugs they studied target more than one property of the bacteria, it may be harder for the microbes to develop resistance to them.
This feature, together with the fact the drugs are already approved, could be a great advantage in the race against time to find new antibiotics as current antimicrobials lose their ability to deal with emerging superbugs.
Study leader Eric Oldfield, a professor of chemistry, says we now have bacteria that are totally resistant to current drugs, and adds:
“They can adapt and find ways around the things we develop to kill them. So if we attack them at multiple targets, it’s harder for them to make one little change to get around it.”
There is a class of drugs called uncouplers – used to treat parasitic infections – that works by sabotaging a cell’s energy supply, triggering shutdown of cellular processes. Interest in seeing if these drugs can be used for the treatment of other diseases, such as diabetes, is growing.
Many FDA-approved uncouplers have antibiotic potential
Given the urgent need for new antibiotics, the team decided to search among uncoupler drugs in development or already available that might have potential use in acting against bacteria.
The team discovered many uncoupler drugs already approved by the Food and Drug Administration (FDA) met their criteria. And not only this, but some had added benefits, as Prof. Oldfield explains:
“What we found is that a lot of FDA-approved molecules that are in use actually do kill bacteria and also act as uncouplers. We were kind of surprised to find that. What’s even better is that some of those molecules also inhibit enzymes specific to bacteria, or disrupt the membrane or the cell wall.”
Vacquinol – a drug that is being developed as a treatment for a brain cancer called glioblastoma – is an example of a drug that they found to have this added enzyme-inhibiting effect. When used against tuberculosis (TB) bacteria, it not only acted as an uncoupler that interrupts the bacteria’s energy supply, but it also blocked an enzyme important for TB virulence.
A further search found more compounds with a similar structure to vacquinol that were effective against the TB bacterium and Staphylococcus aureus, a common cause of infection after injury or surgery.
“It’s a new approach to antibiotics,” Prof. Oldfield notes, “targeting enzymes together with bacterial energy production.”
Compounds that metabolize into uncouplers inside bacteria
The researchers now want to find ways to make compounds that metabolize into uncouplers inside the bacterial cell. This would reduce the chance of the molecules interfering with human cells and the likelihood of the bacteria developing resistance to them.
They hope that some of the compounds that have this property are already approved by the FDA. For example, some heartburn drugs are metabolized within the cell into a molecule that fights tuberculosis.
Prof. Oldfield notes you could screen a million molecules to find a new compound, but you would be unlikely to know how toxic it was.
The alternative, he says, is to start with a compound that is already known. He concludes:
“Once you start making derivatives, you’ll have to prove they’re safe, but there’s a greater chance to get something that’s safe and effective by starting with an approved drug than if you just go into the chemistry lab and screen unknown compounds.”
Meanwhile, Medical News Today recently learned of a study that suggests electrical stimulation may offer an alternative to antibiotics for wound treatment. Researchers from Washington State University found their approach almost completely eliminated a multidrug-resistant bacterium that is often found in hard-to-treat infections.