Our pill-popping culture and over-zealous livestock farmers typically take the blame for the widespread resistance of many harmful strains of bacteria to entire classes of antibiotics.

And the Food and Drug Administration took a bold move today with a new voluntary plan to help curtail the over-use of antibiotics in agriculture.

But the capacity to fend off antibiotics might actually be lodged deep in bacteria's evolutionary history. A new study has uncovered dozens of species of bacteria in a 4 million-year-old cave that harbor resistance to both natural and synthetic antibiotics.

A team of researchers descended to 400 meters in distant, untrafficked reaches of Lechuguilla Cave in New Mexico to collect samples of bacteria. Few people have entered the cave's deepest regions since its discovery in 1986, and surface water takes thousands of years to percolate through the nearby dense Yates Formation rock down to the cave. As a consequence, the area is a prime place to study naturally occurring antibiotic resistance, noted the researchers, whose results were published online April 11 in PLoS ONE.

"Our study shows that antibiotic resistance is hard-wired into bacteria," Gerry Wright, director of McMaster University's Michael G. DeGroote Institute for Infections Disease Research and co-author of the new study, said in a prepared statement. "It could be billions of years old."

Members of this team had also recently shown that there was genetic evidence of antibiotic resistance in soil bacteria from 30,000 years ago. And other studies had found evidence of resistance in life found in the deep ocean and deep below the Earth's surface. In both cases, as with the Lechuguilla Cave, it is unlikely that local bugs could be contaminated by modern-day antibiotics.

Wright and his colleagues found that of the 93 bacterial strains tested from the cave, most were resistant to more than one of the 26 different antimicrobials. And some bacteria were resistant to more than a dozen antibiotics used by doctors, such as telithromycin, ampicillin and daptomycin, which is currently a treatment of last resort to combat resistant infections. The cave bacteria were not likely to cause infection in humans, but could provide the genetic traits that confer resistance to that are.

The finding hardly exonerates humans for our role in creating conditions that exert a strong selective pressure on bacteria to become tolerant and resistant to antibiotics. But it does mean that pathogenic drug-resistant bacteria might deploy genetic traits that were already circulating in the environment and put them to use against our pharmaceutical armamentarium. "Most practitioners believe that bacteria acquire antibiotic resistance in the clinic," Wright said. "The actual source of much of this resistance are harmless bacteria that live in the environment," responding to naturally occurring antibacterials.

"This has important clinical implications," Wright said. "It suggests that there are far more antibiotics in the environment that could be found and used to treat currently untreatable infections."

In addition to familiar patterns of resistance, the researchers also discovered a new mechanism of resistance, suggesting that more drug-evading tricks might be waiting in nature's wings. "This fact further underlines the importance of judicious use of antibiotics," the researchers wrote in their paper.