Ancient bacteria from 5,000-year-old ice reveals clues to fighting superbugs

A team of Romanian scientists drilled a 25-metre ice core from the Scǎrișoara Cave in search of clues for developing new medicines. The 5,000-year-old ice yielded samples of ancient bacteria.

Laboratory analysis revealed something remarkable. These bacteria, undisturbed for thousands of years, were able to grow in a variety of harsh environments. They thrived in extreme cold and high salt levels; settings that would normally prevent bacterial growth.

The scientists also discovered that the ancient bacteria were resistant to ten modern antibiotics, including powerful broad-spectrum treatments such as ciprofloxacin – drugs designed to kill many types of bacteria. In other words, the antibiotics that would normally kill bacteria or halt their growth were largely ineffective against this strain.

How can bacteria evolve resistance to antibiotics long before scientists have created them or doctors have prescribed them?

The answer to this apparent conundrum lies in the fact that all modern antibiotics trace their origins back to nature. For billions of years, bacteria have been engaged in an evolutionary struggle with each other. They have produced formidable chemical attack-and-defence mechanisms as a result.

A deeper understanding of these mechanisms has the potential to help scientists discover new antibiotics to treat dangerous infections. The natural environment is densely packed with bacteria and other microbes. There is strong competition for the limited space and nutrients it provides.

Many species produce chemical compounds that kill or suppress nearby rivals. This gives them an advantage in the struggle for these resources. But the defensive chemicals they generate drive adaptation. Bacteria must protect themselves from their own toxins. Meanwhile, competitors evolve ways to withstand them.

Over billions of years, this arms race has generated an enormous reservoir of resistance genes and antimicrobial compounds.

The number of biological processes inside bacteria that antibiotics can target is limited. Yet the diversity of this natural resistance is so great that some scientists argue genes capable of resisting all future antibiotics may already exist in the environment.

The samples recovered from the Romanian ice cave offer a powerful example of this idea. The bacteria had been sealed off from the outside world for 5,000 years. Yet they were still able to demonstrate resistance to several important modern medicines. This included those used to treat severe and potentially fatal infections like tuberculosis.

There is no evidence that the microbes from the cave are harmful to humans. But bacteria do not exist in isolation. They have a remarkable ability to share useful traits with one another by exchanging small pieces of DNA, even between unrelated bacterial species. This means that resistance genes preserved in environmental bacteria do not necessarily stay there. There is a risk that if these genes pass to disease-causing bacteria, existing drugs could become less effective.

Rising temperatures are accelerating the melting of global land ice. There is a danger that long-dormant microorganisms and their genetic material could be released into the soil and water systems.

If resistance genes that have been preserved for thousands of years re-enter modern microbial communities, they could contribute to the spread of global antibiotic resistance. This would make the treatment of both common and serious bacterial infections much more difficult.

Nature’s hidden pharmacy

However, the same evolutionary pressures that drive resistance also lead microbes to produce molecules capable of killing rival bacteria.

In laboratory tests, chemicals produced by the ice cave samples were able to kill or inhibit 14 different types of bacteria known to cause human disease. This included several that are on the World Health Organization list of high-priority pathogens.

These compounds could provide starting points for the development of new antibiotics. They could help overcome existing drug resistance in harmful bacteria.

Many of today’s antibiotics were originally discovered by studying natural microbes. Penicillin is one example.

Most bacteria preserved in ancient environments remain unstudied. They may represent an important and largely untapped source of new antimicrobial compounds.

The ice cave bacteria’s DNA also contains numerous genes with no clearly identified role. These unknown sequences may represent biochemical capabilities that have never been characterised.

They offer potential not only in medicines discovery, but also in areas as diverse as industrial biotechnology. For example, enzymes that enable the bacteria to function in extreme cold could be adapted for use in industrial processes that run at lower temperatures. This could improve energy efficiency and reduce costs.

The bacteria preserved in Romanian ice illustrate how deeply rooted antibiotic resistance is within the natural world. They also demonstrate how much of nature’s chemical diversity remains unexplored.

Ancient microbes may contain potentially harmful antibiotic resistance genes that warrant careful global monitoring. But they also contain a vast store of biochemical tools that could provide us with new medicines.

As antimicrobial resistance continues to rise worldwide, understanding these ancient microbial systems may prove increasingly important.

Matthew Holland receives funding from the Engineering and Physical Sciences Research Council (EPSRC) and the Ineos Oxford Institute.