AI discovers new elegance of antibiotics to kill drug-resistant micro organism

Artificial intelligence has helped discover a new class of antibiotics that can treat infections caused by drug-resistant bacteria. This could help in the battle against antibiotic resistance, which was responsible for killing more than 1.2 million people in 2019 – a number expected to rise in the coming decades.

Testing in mice showed that the new antibiotic compounds proved promising treatments for both Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus – a bacterium that has developed resistance to the drug typically used for treating MRSA infections.

“Our [AI] models tell us not only which compounds have selective antibiotic activity, but also why, in terms of their chemical structure,” says Felix Wong at the Broad Institute of MIT and Harvard in Massachusetts.

Wong and his colleagues set out to show that AI-guided drug discovery could go beyond identifying specific targets that drug molecules can bind to, and instead predict the biological effect of entire classes of drug-like compounds.

First, they tested the effects of more than 39,000 compounds on Staphylococcus aureus and three types of human cells from the liver, skeletal muscle and lungs. The results became the training data for AI models to learn about the patterns in each compound’s chemical atoms and bonds. That allowed the AIs to predict both the antibacterial activity of such compounds and their potential toxicity to human cells.

The trained AI models then analysed 12 million compounds through computer simulations to find 3646 compounds with ideal drug-like properties. Additional calculations identified the chemical substructures that could explain each compound’s properties.

By comparing such substructures in different compounds, the researchers identified new classes of potential antibiotics and eventually found two non-toxic compounds capable of killing both MRSA and vancomycin-resistant Enterococci.

Finally, the researchers used mouse experiments to demonstrate the effectiveness of these compounds in treating skin and thigh infections caused by MRSA.

Only a few new classes of antibiotics, such as oxazolidinones and lipopeptides, have been discovered that work well against both MRSA and vancomycin-resistant Enterococci – and resistance against such compounds has been increasing, says James Collins at the Broad Institute, a co-author of the study.

“Our work identifies a new class of antibiotics, one of the few in 60 years, that complements these other antibiotics,” he says.

The researchers have begun using this AI-guided approach for designing entirely new antibiotics and discovering other new drug classes, such as compounds that selectively kill ageing, damaged cells involved in conditions such as osteoarthritis and cancer.