Researchers Find Antibiotic Resistance in Ancient DNA

By NICHOLAS WADE

Published: August 31, 2011

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An analysis of 30,000-year-old bacteria whose DNA has been recovered from the Yukon permafrost shows that they were able to resist antibiotics.

Antibiotics, before they became used as drugs, were natural products. The new finding is the first direct evidence that antibiotic resistance is a widespread natural phenomenon that preceded the modern medical use of antibiotics.

Experts had long predicted this on theoretical grounds, but they say the new finding underlines the need to use antibiotics sparingly, given that the genes for antibiotic resistance are ubiquitous and can easily be promoted by antibiotics.

“The fact that the genes for resistance are so ancient and widespread means there is no easy solution to the problem of resistance — we will never invent a super-antibiotic that clears everything up,” said Martin J. Blaser, a microbiologist at New York University.

DNA from the ancient bacteria was analyzed by Gerard D. Wright of McMaster University in Ontario. A colleague who works on ancient DNA, Hendrik N. Poinar, told him of a site at Bear Creek in the Yukon Territory in Canada where ancient DNA could be found uncontaminated by anything from the modern world.

Dr. Wright’s team gathered DNA from a layer of mud about 20 feet beneath the surface. The mud was once the sediment around the edge of an ancient lake. Right above the mud layer lies a layer of volcanic ash deposited 30,000 years ago. The site had evidently been shielded from contamination because it contained DNA from ice-age animals like the mammoth, and none from contemporary species like elk or moose.

The ancient bacteria in the sediments turned out to contain all the major genes that enable modern bacteria to resist antibiotics, Dr. Wright reports in Thursday’s issue of the journal Nature. He and his team grew the products specified by some of these ancient genes, showing that the resurrected proteins conferred resistance to antibiotics.

Antibiotics are substances produced by fungi, algae and bacteria for signaling and for defense. The inhabitants of this microbial world have also evolved genes that counteract antibiotics. After millions of years of chemical warfare, two classes of sophisticated genes have emerged, those that make antibiotics and those that provide resistance to antibiotics.

“Antibiotic resistance is part of the natural ecology of the planet, and this finding is a cautionary note about how we use these things,” Dr. Wright said. “Antibiotics are remarkable resources that need to be carefully husbanded.”

Widespread use of the drugs has promoted the development of bacteria that have become the scourge of hospitals because they can resist many different kinds of antibiotic. “What this finding says to me is that we have to use the antibiotics we have prudently, because we’re not going to get away with misuse,” said Stuart Levy, a microbiologist at Tufts University who has warned of profligate use of antibiotics for 30 years.

“What had been missed in the 1960s and 1970s was the ease with which resistance could appear,” he said. “Bacteria share these genes like baseball cards with each other.” Most physicians in the United States are now prescribing antibiotics more discriminately, in Dr. Levy’s view, but the drugs are overused in poor countries and by farmers who feed millions of pounds of antibiotics to farm animals because they induce quicker growth.

The drugs promote the emergence of drug-resistant bacteria both in the animals and in the farm workers, Dr. Levy said. “It’s almost an embarrassment that we are still using antibiotics in animal feed for growth promotion when all of Europe has abandoned the practice,” he said.

New methods of DNA sequencing have enabled researchers to study more deeply the communities of bacteria that live in the human gut. The bacteria are noticed only when troublesome, but researchers now believe that in normal times they perform many protective duties.

This raises the question of whether the protective bacteria may be harmed when a person takes a course of antibiotics.

Dr. Blaser warned in an article in Nature last week that the natural bacterial community of the human gut, handed down from mother to child over thousands of generations, might have been severely degraded in the antibiotic era. He sees a possible connection between this impoverishment of human gut bacteria and the current epidemic of obesityin wealthy countries. Farmers feed antibiotics to promote animal growth, and the same thing may be happening inadvertently to the human population, Dr. Blaser wrote.

The discovery that the bacteria of 30,000 years ago had genes for antibiotic resistance underlines the danger of looking at bacteria from a purely medical perspective. Resistance to antibiotics is a defense that bacteria have developed in an arms race that has gone on for a billion years.

“Our use and overuse of antibiotics is amplifying the phenomena dramatically,” Dr. Blaser said.A version of this article appeared in print on September 1, 2011, on page A12 of the New York edition with the headline: Researchers F
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.nytimes.com/2011/09/01/science/01gene.html