Hedgehog bacteria became resistant to antibiotics on its own

Deep between the spines of hedgehogs live bacteria that are resistant to antibiotics. It is a methicillin-resistant strain of Staphylococcus aureus, or MRSA. Such bacteria are notorious in hospitals because they can make patients very ill and are difficult to combat.

Scientists always thought that MRSA bacteria evolved in response to the overuse of methicillin in medicine, since the 1960s. But they also live on the backs of hedgehogs in nature. A large international team led by Danish and British biologists dated the emergence of this resistance at least 200 years ago, well before the discovery of antibiotics. The study was published last week in the magazine Nature.

Genetic sifting

The hedgehog bacteria developed their antibiotic resistance during a so-called ‘evolutionary arms race’, namely in competition with fungi that also live between the hedgehog spines. Those fungi protect themselves against bacteria by producing two bacteria-inhibiting substances. These are so-called beta-lactams, a group of antibiotics that also includes penicillin, methicillin and amoxicillin. The hedgehog bacteria did not let this happen: they developed resistance to it, thanks to natural selection.

There are several strains of MRSA. The hedgehog version owes its resistance to the mecC gene. This codes for an enzyme that binds to beta-lactams and thus blocks their action. This mecC-MRSA is also observed in hospitals and accounts for about 0.5 percent of the infections there.

After genetically sifting through MRSA from hedgehogs, cattle and humans, the researchers suggest that the mecC-MRSA was transferred from the hedgehogs to humans via cows. Previous research had shown that livestock and various wild animals can carry mecC-MRSA, but until now it was thought that they would have gotten it from humans and not the other way around. The researchers suspect that the majority of MRSA strains originated in humans.

This is exciting research. Very cool to see

Daniel Rozen senior lecturer

“This is very exciting research,” responds Daniel Rozen, senior lecturer at Leiden University. He specializes in evolution and competition in micro-organisms, but was not involved in it himself Nature-research. “Antibiotic resistance has not often been explored in such detail, and dated so precisely. And then also with hedgehogs, nice animals. Not just anywhere in a forest floor. Very cool to see.”

This is not the first antibiotic resistance to be found in nature, Rozen emphasizes. It is present everywhere, even far from human influences: in soils, caves and swamps and even in Antarctica. “There are micro-organisms everywhere, and everywhere they produce substances with which they defend themselves against other micro-organisms.” The resistance does not only concern methicillin and other beta-lactams, but a very broad spectrum of substances – and it therefore does not only concern the bacteria S. aureus.

Evolutionary history

It is therefore in fact a coincidence that this MRSA strain, which is relevant to us, apparently only emerged around 1800: very recent in evolutionary history. “There are all kinds of lines of bacterial antibiotic resistance that go back millions of years,” Rozen says. “So there are probably more resistant strains of bacteria that can also infect humans in nature. At least we know that MRSA has been found in all kinds of wild animals, including rabbits and birds. But it has now been determined exactly where and when that resistance arose in these hedgehogs, and the direction in which those bacteria have jumped to other organisms.”

Meanwhile, researchers worldwide are frantically searching for new natural antibiotics using modern genetic techniques. These could help in the fight against MRSA in hospitals. They don’t necessarily have to search in new places, or in new organisms, says Rozen. “The production of antibiotics appears to be a matter of turning on certain genes,” he says. “Antibiotic genes make up a large part of the genome of many microorganisms, but they often go unused. The microorganisms only turn them on when necessary, often in competition with other organisms. We investigate when and why they do this, and how we can influence that.”

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