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AI-driven research is revolutionizing antibiotic discovery by identifying compounds like semapimod that can fight dormant bacteria and break through the defenses of resistant Gram-negative bacteria. Credit: SciTechDaily.com
Most antibiotics target metabolically active bacteria, but using artificial intelligence, researchers can efficiently screen for compounds that are lethal to dormant microbes.
Since the 1970s, there has been a lull in modern antibiotic discovery. The World Health Organization has now declared the antimicrobial resistance crisis as one of the top 10 global public health threats.
If you treat an infection repeatedly, there is a risk that the bacteria will become resistant to antibiotics. But why do infections recur after appropriate antibiotic treatment? One well-documented possibility is that bacteria become metabolically inactive and respond only to metabolic activity. This means that most of the antibiotics are evading detection. After the danger passes, the bacteria come back to life and the infection returns.
From time-lapse microscopy video of E. coli cells treated with semapimod in the presence of SYTOX Blue.Credit: Image courtesy of researcher
The role of AI in antibiotic research
“Resistance is becoming more common over time, and the recurrence of infections is due to this dormancy,” says Jackie Valeri, a former MIT Takeda researcher. Massachusetts Institute of Technology Abdul Latif Jameel (Clinic for Machine Learning in Health) recently completed his PhD in bioengineering at the Collins Institute. Valeri is the lead author of a new paper published in this month's print edition. cell chemical biology it shows how to machine learning It could be useful in screening for compounds that are lethal to dormant bacteria.
Stories of the “sleeper-like” resilience of bacteria are hardly new to the scientific community. An ancient strain of bacteria dating back 100 million years has recently been discovered living in an energy-saving state on the ocean floor of the Pacific Ocean.
James J. Collins, director of the MIT Jameel Clinic's Division of Life Sciences and Termeer Professor of Biomedical Engineering Sciences in the MIT Institute for Biomedical Engineering Sciences and Department of Bioengineering, recently used AI to develop new classes of antibiotics. The discovery of this substance became a hot topic. This is part of the group's larger mission to use AI to dramatically expand the range of existing antibiotics available.
Challenges in the fight against bacterial resistance
According to a paper published by lancetin 2019, found that 1.27 million deaths could have been prevented if infectious diseases were more susceptible to drugs, and one of the many challenges facing researchers is The goal is to find antibiotics that can target bacteria.
In this case, researchers at the Collins Institute used AI to speed up the process of discovering antibiotic properties from known drug compounds. With millions of molecules, this process can take years, but thanks to AI's ability to perform high-throughput screening, researchers identified a compound called semapimod over the course of a weekend. I was able to do.
Time-lapse microscopy video of E. coli cells treated with semapimod in the presence of SYTOX Blue.Credit: Image courtesy of researcher
Dual functionality of Semapimod
Researchers found that semapimod, an anti-inflammatory drug commonly used for Crohn's disease, was also effective against the stationary phase. Escherichia coli and Acinetobacter baumannii.
Another revelation was the ability of semapimod to disrupt the membranes of so-called “gram-negative bacteria.” Gram-negative bacteria are known to have a high inherent resistance to antibiotics because their outer membranes are thick and difficult to penetrate.
Examples of gram-negative bacteria include: Escherichia coli, A. Baumani, Salmonellaand pseudomonisall of which are difficult to find new antibiotics.
“One way to elucidate the mechanism of sema” [sic] It's that the structure was very large and reminded us of other things that target the outer membrane,” Valeri explains. “When you start working with a lot of small molecules…to our eyes, it looks like a pretty unique structure.”
By destroying components of the outer membrane, semapimod sensitizes Gram-negative bacteria to drugs that are normally active only against Gram-positive bacteria.
Valeri recalls a quote from a paper published in 2013. trend biotechnology: “Gram-positive infections need better drugs, but Gram-negative infections need any drug.”
Reference: “Discovery of antibiotics that selectively kill metabolically dormant bacteria”, Erica J. Zheng, Jacqueline A. Valeri, Ian W. Andrews, Aarti Krishnan, Parijat Bandyopadhyay, Melis N. Anahtar, Alice Herneisen , Fabian Schulte, Brooke Linnehan, Felix Wong, Jonathan M. Stokes, Lars D. Renner, Sebastian Lourid, James J. Collins, November 28, 2023. cell chemical biology.
DOI: 10.1016/j.chembiol.2023.10.026
