Published in The Hindu on September 1, 2011

When did bacteria develop antibiotic resistance for the very first time? Of course, it was after the discovery and widespread use, and more often misuse, of antibiotics. This is the cornerstone of antibiotic resistance science.

The premise

Since the discovery of antibiotics has being recent, no more than 70 years ago, antibiotic resistance seen in microbes should be a “modern phenomenon.”

By extension, any microbes older than 70 years should be “highly susceptible to antibiotics,” and hence should never have shown antibiotic resistance.

But a study published today (September 1) in Nature , rocks the very foundation of our understanding of antibiotic resistance. It provides sufficient evidence to prove that antibiotic resistance is a “natural phenomenon,” and existed in microbes predating antibiotic discovery by man.

Earlier studies had estimated that origin of natural antibiotics dates back from 2 billion years to 40 million years ago. If natural antibiotics were that old, can antibiotic resistance be far behind?

Antibiotic resistance seen in microbes (bacteria and fungi) should not be a surprise as they produce antibiotics naturally. “Roughly 80 per cent of antibiotics currently in the market are derived either directly or indirectly (e.g. by modification of naturally occurring structures) from bacteria that are found in the environment, mostly the soil,” stated Gerard D. Wright from McMaster University, Hamilton, Canada in an email to this Correspondent. Dr. Wright is the senior author of this study.

Shocking

What makes the findings all the more surprising is that all the genes extracted from nearly 30,000-year-old microbes reveal the presence of resistance to many commonly used antibiotics — tetracycline, beta-lactam, glycopeptides and even vancomycin.

In clinical settings, vancomycin resistance was first seen in pathogenic bacteria (enterococci) only in the late 1980s!

“Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants,” the authors write.

If bacteria already had antibiotic resistance towards drugs like tetracycline, Vancomycin, beta-lactum etc used today, why did it take some time for antibiotic resistance to show up in clinical settings?

“We need to differentiate resistance in pathogenic bacteria here from [benign] environmental bacteria that do not usually cause disease,” replied Dr. Wright. “Pathogens are generally quite antibiotic sensitive unless they acquire resistance genes from other sources.

“The evidence suggests that environmental bacteria are the reservoir for these genes. Our study demonstrates that these benign bacteria have expressed these genes for millennia.”

The widespread prevalence of antibiotic resistance seen today “is inconsistent with a hypothesis of contemporary emergence,” they write in the paper, “instead it suggests a richer natural history of resistance.”

So what is the role of clinically formed resistance? “The clinical (and other use) of antibiotics provides the selective pressure to select for resistance genes that may be mobilised from environmental bacteria,” emphasised Dr. Wright in his email.

What needs to be done

If this is indeed true and correct, then there is an overwhelming need to have in place a more responsible planning and management mechanism of existing antibiotics and newer ones.

According to Dr. Wright, “we need two things: 1) more drug candidates, and 2) better use of existing antibiotics e.g. reduced use in agriculture, and tight controls in medicine.”

Study area

The microbes used for the study were collected from Dawson City, Yukon, Beringia (east of Alaska) permafrost sediments. Rigorously authenticated ancient bacterial DNA samples were used for the study. The ancient DNA was collected from the permafrost that had not thawed since its deposition, and had never been leached by a river.