Metal-based compounds may be the future of antibiotics

Scientists are putting the pedal to the metal to develop new antibiotics. Metal-based drugs can open a new world of medicine, especially as antimicrobial resistance is growing. Researchers have also found a way to create and test these metal compounds much faster than before through the use of robots.

Metallic medicine

Robotic chemistry can be used to produce and test metal-based antibiotics, according to a study published in the journal Nature Communications. Most modern antibiotics are organic or carbon-based and tend to interact with bacteria in predictable ways. However, metal-containing compounds have a unique geometry that “allows them to interact with bacteria in completely different ways, potentially overcoming the resistance mechanisms that defeat current drugs,” said a release about the study.

Researchers used robots and “click chemistry,” a “method where two molecular components are ‘bolted’ together efficiently,” to produce over 600 compounds, said the release. “We opted to use liquid-handling robots to do the chemistry because it’s just combining different reagents in the right ratios," Angelo Frei, the lead author of the study, said to Live Science. This method allowed for the rapid testing of the compounds, turning months of work into just days, though careful checks were still required.

An iridium metal complex was specifically identified as a promising antibiotic drug. It “demonstrated high effectiveness against bacteria, including strains similar to the deadly MRSA (Methicillin-resistant Staphylococcus aureus), while displaying low toxicity to human cells,” said the release. The compound “was about 50 to 100 times more active against bacteria than it was toxic to human cells,” a difference that is “vital to ensure that the complex is simultaneously effective in treating an infection but safe to use on human tissues,” said Live Science.

Revved-up research

The findings come at a time when antibiotic resistance is becoming more of a danger. “The pipeline for new antibiotics has been running dry for decades,” Frei said in the release. “Traditional screening methods are slow and the pharmaceutical industry has largely withdrawn from this space due to low returns on investment. We have to think differently.” Different metal compositions “can hit bacteria in several ways, which matters when single-target drugs stop working,” said Earth.com. A metal center “can change its charge and grip key bacterial proteins, which can stall processes needed for growth.”

There has been a “misconception that metal-based drugs are inherently toxic,” said the release. However, “metal complexes actually have a higher ‘hit rate’ for being antibacterial without being toxic compared to standard organic molecules.” Still, because bacteria evolve quickly, there is a risk of resistance developing to these compounds over time. The good news is that robotic chemistry can significantly speed up research. “The iridium compound we discovered is exciting, but the real breakthrough is the speed at which we found it,” Frei said. “This approach could be the key to avoiding a future where routine infections become fatal again.” The method can also be used beyond antibiotics and help further several areas of biomedical research.