Alexandra Ferguson
(CNN) Researchers have found a new type of antibiotic that works against a particularly dangerous and drug-resistant bacterium, thanks to artificial intelligence.
When they tested the antibiotic on the skin of mice experimentally infected with the superbug, the growth of the bacteria was controlled, suggesting that the method could be used to create antibiotics tailored to fight other drug-resistant pathogens.
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The researchers also tested the antibiotic against 41 different antibiotic-resistant strains of Acinetobacter baumannii. The drug worked in all of them, although it would have to be perfected and tested in human clinical trials before it could be used in patients.
What’s more, the compound identified by the artificial intelligence worked in a way that only blocked the offending pathogen. It does not appear to kill the many other species of beneficial bacteria that live in the gut or on the skin, making it a rare and limited-acting agent.
According to the researchers, if there were more antibiotics that worked with this precision, bacteria could be prevented from becoming resistant.
The study was published in the academic journal Nature Chemical Biology.
“It’s incredibly promising,” says Dr. César de la Fuente, an associate professor at the University of Pennsylvania Perlman School of Medicine, who is also using AI to find new treatments but was not involved in the new research.
De la Fuente says this type of approach to finding new drugs is an emerging field that researchers have been testing since about 2018. It dramatically reduces the time it takes to screen thousands of promising compounds.
“I think AI, as we’ve seen, can be successfully applied in many domains, and I think drug discovery is kind of the next frontier.”
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For the study, the researchers focused on the bacterium Acinetobacter baumanii. This bacterium is present in hospitals and other health centers and adheres to surfaces such as doorknobs and counters. Because he is able to take bits of DNA from other organisms he comes into contact with, he can incorporate their best weapons: genes that help them resist the agents doctors use to treat them.
“It’s what we in the lab call a professional pathogen,” says Jon Stokes, one of the researchers and an assistant professor of biochemistry and biomedical sciences at McMaster University in Hamilton, Ontario.
This species causes skin, blood or respiratory infections that are difficult to treat. The US Centers for Disease Control and Prevention (CDC) noted in 2019 that Acinetobacter baumanii infections were “most in need” of new types of antibiotics to treat them.
A recent study of hospitalized patients with Acinetobacter baumanii infections resistant to even powerful carbapenem antibiotics found that 1 in 4 had died within a month of diagnosis.
For the new study, Stokes and his lab collaborated with researchers at MIT’s Broad Institute and Harvard. First, they used a technique called high-throughput drug screening to grow Acinetobacter baumanii in laboratory dishes, spending weeks exposing these colonies to more than 7,500 agents: drugs and active drug ingredients. They found 480 compounds that blocked the growth of the bacteria.
They fed that information into a computer and used it to train an artificial intelligence algorithm.
“Once we had our model trained, what we could do was start showing it new images of chemicals that it had never seen before, right? And based on what he had learned during training, he would predict to us whether or not those molecules were antibacterial,” explains Stokes.
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They then had the model analyze more than 6,000 molecules, which Stokes said the AI was able to do in a few hours.
They narrowed the search to 240 chemicals, which they tested in the lab. Laboratory tests helped them narrow the list down to nine of the best inhibitors of the bacteria. From there, they took a closer look at the structure of each one, eliminating the ones they thought might be dangerous or related to known antibiotics.
They were left with a compound, called RS102895, which Stokes believes had originally been developed as a possible treatment for diabetes.
According to Stokes, it appears to work in a completely new way, by preventing components of the bacterium from moving from inside the cell to its surface.
“This is quite an interesting mechanism that, to my knowledge, is not seen among clinical antibiotics,” he says.
In addition, RS102895—referred to by researchers as abaucin—only works against Acinetobacter baumanii.
According to Stokes, most antibiotics are broad-spectrum and work against many species of bacteria. Broad-spectrum antibiotics exert huge selection pressure on many types of bacteria, causing many to evolve rapidly and share genes that help them resist the drug and survive.
“In the case of this molecule, since it only works very potently against Acinetobacter, it doesn’t impose that universal selective pressure, so it won’t spread resistance as quickly,” he explains.
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