Antibiotics created from extinct species could fight infections

Molecules from the bodies of extinct species including the woolly mammoth and giant sloth have been resurrected and found to fight infections.

In an effort to discover new antibiotics, scientists used AI to mine the biological data of long-dead species, in the hope of finding lost fragments that could be repurposed.

The Machine Biology Group, at the University of Pennsylvania, discovered more than 11,000 sequences that are not present in species today and synthesised 69 potential antibiotics from the information.

When they tested the extinct molecules on infected mice, several were shown to work as well as traditional antibiotics, reducing bacterial load significantly.

Promising compounds were found in the woolly mammoth, Steller’s sea cow, the straight-tusked elephant, the giant elk (also known as the Irish elk) and the giant sloth.

Dr Cesar de la Fuente-Nunez, who leads the Marine Biology Group, said: “Previously we had developed algorithms to mine the human genome and human proteome for a source of antibiotics and we had previously found antibiotics in the human body, which led us to [the] hypothesis that they would be conserved across evolution.

“We found antimicrobial compounds in Neanderthals and that gave us the confidence to challenge ourselves and say why not go after every extinct organism known to science to see if we can find antibiotic molecules in there.

“We term it molecular de-extinction and we’re proposing to bring back molecules from the past to address 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 of breast cancer.

Health experts have warned that within 20 years even routine operations such as hip replacements and organ transplants could be deadly 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 proteome of extinct species – the proteome being the complete set of proteins expressed by an organism.

Apex searched through the entire catalogue of extinct species, including ancient penguins, lost magnolia trees and extinct bears before picking out several areas that looked hopeful.

While traditional methods of finding antibiotics can take years or decades, the team had results within the first day of running the programme.

“We train our model to target a particular pathogen, and the algorithm is able to run through all that code and work out if any of it would make a good biological agent,” said Dr de la Fuente-Nunez.

“Traditional methods rely on going around nature and taking samples from soil and trying to purify in the laboratory, which takes many many years, but now with the computer, we can come up with hundreds of thousands.

“We synthesised dozens of them and validated them in vitro in the laboratory and many of them were highly effective in mouse models, with the mammoth, and ancient elk and giant sloth being the most effective.

‘Could help save lives’

The most promising antibiotics compounds found are mammuthusin-2, from the woolly mammoth, mylodonin-2 from the giant sloth and megalocerin-1 from the giant elk.

In experiments, mice were infected with A.baumannii – a bacteria that often infects burns victims. Two days after treatment with mylodonin-2, the mice showed similar results 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 mammoth and megalocerin-1 from the giant elk.

Intriguingly, the ancient antibiotics work in a different way to traditional drugs, which usually target the outer membrane, killing the bacteria by depolarising the membrane. Polarisation is crucial to cell function.

The team believes the compounds might have once helped keep ancient animals alive before they became extinct.

Dr de la Fuente-Nunez added: “We were incredibly excited to tap into the 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 make it into the clinic, that would be a dream future if one could help save lives.”

On Friday, the World Health Organisation (WHO) issued a report on antibiotics warning there is a ‘pressing need’ for new, innovative agents to fight serious infections and replace drugs that are becoming ineffective.

Dr Yukiko Nakatani, WHO’s assistant director-general for antimicrobial resistance, said: “Antimicrobial resistance is only getting worse yet we’re not developing new trailblazing products fast enough to combat the most dangerous and deadly bacteria.

“Innovation is badly lacking yet, even when new products are authorised, access is a serious challenge. Antibacterial agents are simply not reaching the patients who desperately need them, in countries of all income levels.”

As well as antimicrobial resistance, the team are also keen to use the method to find compounds, which could fight inflammation and cancer or boost the immune system.