Superbugs, or enterococci bacteria, have been honing their defensive capabilities for at least 450 million years.

As a new survey of the evolution of antibiotic resistance revealed, the earliest relatives of modern superbugs -- microbes undeterred by antibiotics -- emerged prior to the arrival of the dinosaurs.

"By analyzing the genomes and behaviors of today's enterococci, we were able to rewind the clock back to their earliest existence and piece together a picture of how these organisms were shaped into what they are today," researcher Ashlee M. Earl, leader of the Bacterial Genomics Group at the Broad Institute, said in a news release. "Understanding how the environment in which microbes live leads to new properties could help us to predict how microbes will adapt to the use of antibiotics, antimicrobial hand soaps, disinfectants and other products intended to control their spread."

As detailed in the journal Cell, microbes have been adapting to life on and in animals since the first multicellular organisms emerged some 3.5 billion years ago.

Many bacteria species formed a symbiotic relationship inside animals. Many microbes, like the microbiota found inside intestines, remain vital to animal health. Other microbes took on a more adversarial role, damaging cells and causing disease.

Genomic analysis of enterococci strains suggest the relatives of modern superbugs have been living in the intestines of animals ever since the first animal crawled out of the sea and onto land. Since they first emerged, the microbes have benefited from an innate resistant to difficult conditions.

Even the earliest enterococci, researchers suggest, were able to withstand drought and lack of nutrients, as well as disinfectants and antibiotics.

Unlike most bacteria, which dies once it is excreted out in the form of feces and becomes dehydrated, enterococci perseveres. Life on dry land encourages and rewards hardiness. In the ocean, dehydration isn't in the cards. Microbes simply sink to the bottom and reenter the food chain.

"We now know what genes were gained by enterococci hundreds of millions of years ago, when they became resistant to drying out, and to disinfectants and antibiotics that attack their cell walls," said Michael S. Gilmore, director of the Harvard Infectious Disease Institute.

By understanding the evolutionary origins of enterococci, researchers hope to design more effective disinfectants and antibiotics.

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