Antibiotic-resistant microbes date back 450 million years, study finds

Antibiotic-resistant microbes have an ancestry that dates back hundreds of millions of years, even before dinosaurs roamed our planet, a new study says.

Researchers from the Massachusetts Eye and Ear, the Harvard-wide Program on Antibiotic Resistance and the Broad Institute at MIT released a study on Thursday tracing the evolution of enterococci, a common bacteria. 

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As life forms emerged from the oceans and transitioned from marine animals to land animals, they brought along microbes that adapted to different extreme environments such as cold and starvation, the researchers say. 

As the bacteria adapted, they began to resist things in the natural environment that could kill them, eventually emerging into the microbes we see today.

'Cockroaches of bacteria'

There are about 1,000 different types of bacteria in our gut, most of which are harmless. But there are two types — enterococcus faecalis and enterococcus faecium — that can cause us to become ill. While both may sound similar, they're at opposite ends of the family tree, said Michael Gilmore, co-author of the paper and a senior scientist with the Massachusetts Eye and Ear. 

'Enterococci are like the cockroaches of bacteria.'- Michael Gilmore, director of the Harvard Infectious Disease Institute

An enterococci bacteria infection can cause several health problems, from urinary tract infections to meningitis. Usually these are treatable with antibiotics such as penicillin or vancomycin. However, ever since we began using antibiotic drugs, the microbes have been fighting back, with many developing resistance. They've come to be known as superbugs.

The researchers wanted to determine when antibiotic resistance first occurred in enterococci. Since life began, it has always tried to flourish, and bacteria — of which there are 10³º on our planet — are no different. Except these microbes are especially tough.

"Enterococci are like the cockroaches of bacteria," said Gilmore, who is also the director of the Harvard Infectious Disease Institute. "They're just really, really difficult to kill." 

The researchers traced the evolution of enterococcus, sequencing its genome. They also sequenced the genomes of the branches of the family tree and compared them, trying to determine what was common in all of them. 

What they found was an extra 126 extra genes that enterococci picked up since they branched from vagococcus, back about 450 million years ago.

I can't imagine you can make something for which bacteria cannot overcome. Bacteria live at temperatures and pressures that we wouldn't even dream of.- Gerry Wright,  McMaster University

"We think [vagococcus] arose in the Cambrian Explosion and took up residence in sea animals like fish," Gilmore said. "And then when things started crawling on the land, enterococcus arose. As new ecologies arose, as the planet changed, and new opportunities arose, new microbes arose with larger animals."

In particular, it's the enterococci's hard outer cell wall that makes them so tough and able to build up resistance.

Gerry Wright, director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University, said that microbial resistance is just part of the natural process.

"Resistance, as this study kind of shows you, is really old," he told CBC News. "It's part of the genetic landscape of micro-organisms and has been since the first antibiotics started to be produced.… That keeps growing in pace, as it's part of natural selection."

And it's unlikely that they'll ever stop evolving and developing resistance.

"I can't imagine you can make something for which bacteria cannot overcome," Wright said. "Bacteria live at temperatures and pressures that we wouldn't even dream of. More than 100 degrees Celsius; at the very bottom of the ocean with enormous pressure. They live at the tops of mountains; they circulate in the air. They've colonized the entire planet."

Taking responsibility

While antibiotic resistance can be long established — as this study illustrates — it has been greatly accelerated by overuse of antibiotics. Doctors often prescribe them for viral illnesses, but antibiotics can only fight bacterial infections. As well, the overuse of antibiotics in agriculture is a serious threat. Each time an antibiotic is used, it gives bacteria a chance to develop resistance.

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"The more antibiotics we apply, the more likely resistance is going to emerge," Gilmore said.

Gilmore said that he hopes this discovery will present a new way — targeting those extra 126 genes — to develop new antibiotics (as opposed to those that have been slightly modified from existing antibiotics).

"Resistance is almost inevitable," Gilmore said. "We just have to stay ahead of it.… But we now know why this family became resistant. And why it became such a problem in hospitals and why it resists disinfecting. And now have some targets to shoot at. And that's a step in the right direction."

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