by Molecules from the bodies of extinct species, including the woolly mammal and the resurrected giant, have been found to resist infections.
In an effort to discover new antibiotics, the scientists used AI to mine the biological data of long-dead species, hoping to find lost fragments that could be reused.
The Machine Biology Group, at the University of Pennsylvania, found more than 11,000 sequences not present in species today and synthesized 69 potential antibiotics from the information.
When they tested the expired molecules on infected mice, many were shown to work as well as conventional antibiotics, significantly reducing bacterial load.
Promising compounds have been found in the woolly mammal, the Steller’s manatee, the straight-tusked elephant, the giant elk (also known as the Irish elk) and the giant.
Dr Cesar de la Fuente-Nunez, who heads the Marine Biology Group, said: “Previously we had developed algorithms to mine the human genome and the human proteome for a source of antibiotics and we had previously found antibiotics in the body of the a person, which was the result of us. to [the] hypothesized to be conserved throughout evolution.
“We found antimicrobial compounds in Neanderthals and that gave us the confidence to challenge ourselves and say why don’t you go after every extinct organism known to science to see if we can find antibiotic molecules in them.
“We call it molecular deactivation and we are proposing to bring back molecules from the past to tackle modern problems.”
Antimicrobial resistance is a growing problem. In Britain alone, around 12,000 people die each year from antibiotic-resistant bugs, more than the number who die from breast cancer.
Health experts have warned that even within 20 years routine operations such as hip replacements and organ transplants could be fatal because of the risk of infection.
The team developed a new AI model called Apex, which was trained to look for antibiotic compounds in the proteomes of extinct species – the proteome is the complete set of proteins an organism expresses.
Apex searched through the entire catalog of extinct species, including ancient penguins, lost magnolia trees and extinct bears before picking a few areas that looked promising.
Although conventional methods can take years or decades to find antibiotics, the team had results within the first day of running the program.
“We train our model to target a particular pathogen, and the algorithm is able to run all that code and work out whether any part of a biological agent would make a good one,” said Dr. de la Fuente-Nunez.
“Traditional methods rely on going around nature and taking samples from the soil and trying to purify them in the laboratory, which takes many years, but now with the computer, we can come up with hundreds of thousands.
“We’ve synthesized dozens of them and validated them in vitro in the lab and many of them have been very effective in mouse models, with the giant, and old elk and giant sloth being the most effective.
‘Could help save lives’
The most promising antibiotic compounds found are mammuthusin-2, from the woolly mammal, mylodonin-2 from the giant sloth and megalocerin-1 from the giant elk.
In experiments, mice were infected with A.baumannii – a bacterium that often infects burn victims. Two days after treatment with mylodonin-2, the mice showed results similar to a control group treated with polymyxin – a common antibiotic.
Similar positive results were seen after four days in animals treated with mammuthusin-2, from the woolly mammal and megalocerin-1 from the giant elk.
Interestingly, the ancient antibiotics work in a different way from traditional drugs, which usually target the outer membrane, killing the bacteria by depolarizing the membrane. Polarization is critical to cell function.
The team believes the compounds may have helped keep ancient animals alive before they went extinct.
Dr de la Fuente-Nunez said: “We were very excited to tap into unknown sources of new molecules.
“Antibiotic resistance is one of the greatest threats to humanity. We would love to see if any of them can get into the clinic, it would be a dream future if someone could help save lives.”
On Friday, the World Health Organization (WHO) released a report on antibiotics warning that there is an ‘urgent need’ for new, innovative agents to fight serious infections and replace drugs that are becoming ineffective.
Dr Yukiko Nakatani, WHO Assistant Director-General for Antimicrobial Resistance, said: “Antimicrobial resistance is getting worse but we are not developing new traceable products fast enough to tackle the most dangerous bacteria and is fatal.
“The lack of innovation is still bad, even when new products are authorized, access is a big challenge. Antibacterial agents are not available to the patients who need them most, in countries of all income levels.”
As well as antimicrobial resistance, the team is keen to use the method to find compounds that could fight inflammation and cancer or boost the immune system.
