Ancient Microbes Hidden within Earth Could Yield Potent Tool Against Antibiotic-Resistant Bacteria
In a groundbreaking development, researchers at the University of Pennsylvania have harnessed the power of artificial intelligence (AI) to unearth potential next-generation antibiotics from ancient microorganisms, particularly Archaea. These single-celled microbes thrive in extreme environments such as deep-sea vents, salt flats, and hot springs, offering a promising reservoir of new antibiotics with unique modes of action.
The newly discovered compounds, named "archaeasins," were identified using AI tools, including APEX, developed by de la Fuente's lab. These molecules demonstrated potent activity against drug-resistant bacteria in animal models, with some performing comparably to last-resort antibiotics like polymyxin B.
The research team plans to refine AI models, such as APEX, to consider 3D protein structures for improved predictive accuracy. Long-term safety and efficacy studies are planned before clinical application.
Simultaneously, scientists at MIT have applied generative AI to design new antibiotic compounds structurally distinct from existing drugs and active against difficult pathogens like multi-drug-resistant Staphylococcus aureus (MRSA) and Neisseria gonorrhoeae. By screening over 36 million computationally generated molecules for antimicrobial activity, the team identified promising candidates that appear to kill bacteria by disrupting their cell membranes via novel mechanisms.
This fusion of AI and microbiology is viewed as critical to addressing the urgent public health threat of antibiotic resistance, which the World Health Organization (WHO) warns could make even routine infections life-threatening if new drugs are not found soon.
It's important to note that Archaea, the microorganisms in focus, are distinct from bacteria, plants, animals, and fungi in biochemistry, cell membranes, and overall genetics. Previous efforts to find new antibiotics have focused mostly on fungi, bacteria, and animals. However, the unique biochemistry of Archaea makes them a promising reservoir of new antibiotics that may work differently from existing drugs.
The researchers hope to understand the long-term impact of the archaeasins, with a vision to bring them to human clinical trials. They also plan to improve APEX's capabilities to predict antibiotic candidates based on their structure.
Archaea can exist in extreme conditions like superheated undersea vents, blistering hot springs, and other places with crushing pressures, toxic chemicals, and extreme temperatures. In the initial stage, 80 Archaeasins were tested against a disease-causing and drug-resistant bacterium, with 93% of them carrying out antimicrobial activity against at least one bacterium. When scanned 233 species of Archaea, APEX identified over 12,000 potential antibiotic candidates. Four days into the experiment, all Archaeasins stopped the growth of the drug-resistant bacterium that people often catch in hospitals.
César de la Fuente, a senior author in the study, underlined the importance of studying ancient life forms. This study was published in Nature Microbiology, contributing significantly to the ongoing efforts in the discovery of new antibiotics to combat the growing issue of antibiotic resistance.
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