Matt Clark/McMaster University
McMaster University graduate student Dennis Catactan helped identify a new antibacterial compound.
CNN
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Researchers say they have used artificial intelligence to discover a new class of antibiotics that are particularly effective against threatening drug-resistant bacteria.
When the antibiotic was tested on the skin of mice experimentally infected with superbugs, it inhibited bacterial growth, suggesting that the method could be used to create tailored antibiotics to combat other drug-resistant pathogens. suggested that it could be used.
Researchers also tested the antibiotic against 41 different antibiotic-resistant strains. Acinetobacter baumannii. The drug worked in all patients, but needs to be further refined and tested in human clinical trials before it can be used in patients.
Additionally, the compounds identified by the AI functioned to stop only the pathogen in question. It does not appear to kill many other species of beneficial bacteria that live in the gut or on the skin, making it a rare narrowly targeted drug.
The researchers said that more antibiotics working so precisely could prevent bacteria from becoming resistant in the first place.
The study was published in the journal Nature Chemical Biology.
“This is very promising,” said Dr. Cesar de la Fuente, an assistant professor at the University of Pennsylvania’s Perlman School of Medicine. Although he is using AI to find new treatments, he is not involved in any new research.
De la Fuente said this kind of approach to discovering new drugs is an emerging field that researchers have been experimenting with since around 2018. This greatly reduces the time it takes to screen thousands of promising compounds.
“As we have seen, I think AI can be applied well in many areas. I think drug discovery is kind of the next frontier.”
In this study, the researchers focused on the bacterium Actinetobacter baumannii. It inhabits hospitals and other medical settings, clinging to surfaces such as doorknobs and counters. Being able to grab snippets of DNA from other organisms they come in contact with, they can incorporate genes that help them resist the drugs doctors use to treat them, their best weapon.
“This is what we call professional pathogens in the lab,” said John 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 and respiratory infections that are difficult to treat.In 2019, the U.S. Centers for Disease Control and Prevention identified Acinetobacter baumannii New types of antibiotics are “most needed” to treat infections.
A recent study of hospitalized patients with Actinetobacter baumannii infection, which is also resistant to strong carbapenem antibiotics, found that one in four died within a month of diagnosis.
For the new research, Dr. Stokes and his lab collaborated with researchers at MIT and the Broad Institute at Harvard University. First, they grew Acinetobacter baumannii in laboratory dishes using a technique called high-throughput drug screening and spent weeks exposing these colonies to more than 7,500 drugs (drugs and drug active ingredients). spent. They discovered 480 compounds that inhibit bacterial growth.
They put that information into a computer and used it to train an artificial intelligence algorithm.
“Once you have trained a model, the next thing you can do is start showing it a whole new picture of chemicals that it has never seen before, right? It predicts whether something is antibacterial,” Stokes said.
They then had the model screen more than 6,000 molecules, which Stokes said the AI was able to do over hours.
They narrowed their search to 240 chemicals and tested them in the lab. Laboratory testing has allowed us to narrow down the list to nine of the best inhibitors against bacteria. From there, they took a closer look at each structure and ruled out those they thought could be dangerous or related to known antibiotics.
They were left with one compound called RS102895, which Stokes believes was originally developed as a potential treatment for diabetes.
He said it appears to work in a completely new way, preventing components of the bacterium from moving from inside the cell to the cell surface.
“It’s a pretty interesting mechanism, one that, to my knowledge, has never been observed with clinical antibiotics,” he said.
In addition, RS102895, which the researchers renamed Abaucin, works only on Actinetobacter baumannii, he said.
Stokes said most antibiotics are broad-spectrum drugs and work against many types of bacteria. Broad-spectrum antibiotics put tremendous selective pressure on many types of bacteria, causing them to rapidly evolve and share genes that help many bacteria resist and survive drugs.
“For this molecule, we can’t impose a universal selective pressure because it’s only acting so strongly against Actinetobacter, so resistance doesn’t spread that quickly,” he said.
