Antibiotic resistance is a ticking time bomb for global health that could send us spiraling back into the dark ages of medicine. The race is therefore on for researchers to discover new ways to tackle this growing threat before it’s too late. While it’s not going to solve our problems in the long-term, scientists from The Scripps Research Institute (TSRI) may have just bought us a little more time.
As described in the Journal of the American Chemical Society, they successfully synthesized a new antibiotic based on vancomycin that exhibits impressive potencies against both vancomycin-resistant bacteria and other disease-causing bacteria. Furthermore, the new drug has two independent mechanisms of action, meaning that bacteria are unlikely to rapidly acquire resistance.
Since its introduction in the late 1950s, vancomycin has been an invaluable tool in medicine, effective against a wide range of bacteria including the deadly hospital “superbug” methicillin-resistant Staphylococcus aureus (MRSA). However, over the years, resistance emerged and its usefulness began to wane, prompting researchers to look for effective replacements.
Vancomycin acts by inhibiting bacterial cell wall biosynthesis. It does this by binding to cell wall subunits, preventing their proper assembly and hence leaves the bacteria with altered permeability. Bacteria can become resistant to it with a single amino-acid substitution in the cell wall building blocks that prevents the antibiotic from being able to efficiently bind to them.
Two years ago, a TSRI team led by Dale Boger tweaked vancomycin slightly by altering the cell wall binding pocket. They found that this new drug, termed an analog, could latch on to cell wall subunits in both antibiotic-resistant and antibiotic-sensitive bacteria. However, there was room for improvement, so they experimented by adding a new chemical to the analog. This molecule, called a chlorobiphenyl (CBP), has been previously demonstrated to dramatically boost the activity of this antibiotic against both sensitive and resistant strains.
“To our delight, the combination of these modifications led to an incredibly potent molecule, well beyond anything we had expected,” first author Akinori Okano said in a news release.
In lab studies, the researchers found that the new analog exhibited impressive activity against a wide range of bacteria, including MRSA and vancomycin-resistant enterococci. Furthermore, their results seem to suggest that rather than acting as a general booster of activity, CBP actually adds its own independent mechanism of action which works synergistically with vancomycin.
The researchers are now working towards optimizing the synthesis process so that it can be trialed in animals.