Would it surprise you to learn that some of today’s hardiest “superbugs” arose from bacteria that lived before the dinosaurs?

According to a recent study published in the journal Cell, Enterococcus bacteria evolved nearly 500 million years ago — about the same time that animals first appeared on land.

A second burst of Enterococcus species developed about 250 million years ago, following the Permian extinction event.

Now, enterococci are a leading cause of antibiotic-resistant infections, a growing public health concern.

By tracing their evolutionary history, the study’s authors have found genetic clues that might help scientists develop new ways to combat these resilient pathogens.

“Enterococci are like the cockroach of bacteria — they’re really hard to kill,” Michael Gilmore, PhD, the study leader and principal investigator of the Harvard-wide Program on Antibiotic Resistance, told Healthline.

“But we now know a lot more about why they’re so rugged and what genes make them so rugged,” he added. “That gives us a handful of new targets to shoot at.”

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Enterococci are quite resilient

To learn more about enterococci, Gilmore’s team conducted genetic sequencing on 24 Enterococcus species and five other related species of bacteria.

They also examined how well each species grew under different growth conditions.

“We asked what’s common to all enterococci, and how do enterococci differ from other microbes?” he said. “What we found was that enterococci were much more resistant to a lot of things.”

All enterococci have a natural resistance to dryness, starvation, disinfectants, and certain types of antibiotics. Even enterococci that have never been found in a hospital can resist penicillin.

Some enterococci have acquired a resistance to other types of antibiotics, too.

“Back in the mid-80s, enterococci acquired a resistance to a drug called vancomycin, the last drug we had that would kill the multi-drug-resistant versions of Enterococcus that cause infections in hospitals,” explained Gilmore.

“Since then, we’ve introduced a couple of new antibiotics that could be used to treat vancomycin-resistant enterococci, called daptomycin and linezolid. But enterococci have acquired resistances to those, too.”

Enterococcus is mainly a hospital pathogen,” Gilmore explained.

“A patient will go into the hospital and be treated with an antibiotic for something. But when they take an oral antibiotic, it kills off many of the microbes that are in their gut, including the helpful microbes. And the microbial community of the gut is kind of like a house of cards. If you knock out a few cards from the base, the whole thing falls. That leaves the patient vulnerable to new microbes coming in and setting up shop.”

In those conditions, one antibiotic-resistant enterococcus can quickly multiply and wreak havoc on a patient’s health.

“Maybe just one survives in the patient’s gut but finds a place to hang out. It can very quickly become a billion. And once they reach those kind of numbers, they can leak into the bloodstream, or get into the urinary tract, or contaminate a surgical wound. Those are all the kinds of infections that it causes in a hospital,” warned Gilmore.

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Antibiotic resistance is a growing problem

Antibiotic-resistant infections are on the rise, and healthcare providers are running out of treatment options.

Earlier this spring, the World Health Organization (WHO) released a list of antibiotic-resistant bacteria that pose a significant threat to human health.

Vancomycin-resistant Enterococcus faecium was only one of 12 “priority pathogens” on that list.

According to David Weiss, PhD, director of the Emory Antibiotic Resistance Center, a number of factors have contributed to the rise of antibiotic resistance.

“There is an immense evolutionary pressure on the bacteria to resist antibiotics, and they have a multitude of ways to become resistant,” Weiss told Healthline.

“In addition, antibiotics have been overused. Every time an antibiotic is used, it’s an opportunity for bacteria to become resistant. So, unfortunately, increased use leads to increased resistance. This includes over-prescription, both in hospitals and in the outpatient setting. It also includes the use of sub-lethal levels of antibiotics in livestock feed.”

To address this problem, experts advocate limiting the use of antibiotics to cases when they are truly needed and investing in the development of new treatments.

“Greatly expanded funding for basic research is critical to pursue a wide array of leads and identify new antimicrobials as quickly as possible,” Weiss suggested.

Gilmore and colleagues hope their research can support these efforts.

“We sequenced the genomes of these microbes and found that all enterococci have learned 126 new tricks since diverging from Vagococcus, the microbe from which they evolved,” Gilmore said.

“So now we can match up these genes, these 126 new tricks, to all the things that enterococci are resistant to. And we can try to find ways to make them unresistant. That’s our goal, is to come up with new ways to treat these infections, by understanding the very nature of the microbes.”

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