Bacteria: resisting antibiotics since at least 30,000 BC

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The rise of drug-resistant bacteria is one of the most important threats facing modern medicine. One by one, our arsenal of antibiotics is coming up short against microbes that can pump them out, slip under their notice, deactivate them, or even eat them. But these tricks aren’t new. Bacteria have been defeating antibiotics for millennia, long before Alexander Fleming noticed a piece of mould killing off bacteria in a Petri dish. And the best proof of that longstanding struggle has just emerged from the ice-fields of Alaska.

In 30,000-year-old samples of frozen soil, Vanessa D’Costa and Christine King from McMaster University have found a wide variety of antibiotic-resistant genes. They would have allowed ancient bacteria to shrug off many modern drugs such as tetracyclines, beta-lactams and vancomycin.

Vancomycin resistance is especially interesting. This drug has traditionally been used as weapon of last resort, a drug to use when all others have failed. When vancomycin-resistant bacteria first emerged in 1987, it was a surprising blow. Since then, resistant versions of more common bacteria, such as staph (VRSA) have reared their heads.

These superbugs neutralise vancomycin using a trio of genes known collectively as vanHAX. Together, they alter the protein that’s attacked by the drug, rendering it useless. D’Costa and King found that their ancient sequences include the entire vanHAX cluster. They even resurrected these ancient genes, created proteins from them, and showed that they have the same shape, and do the same thing, as their modern counterparts.

D’Costa and King write that their results disprove the idea that antibiotic resistance is a modern phenomenon. Instead, it’s been part of bacterial life long before the modern use of antibiotics. But I’m really not sure how many people would still hold to that view. First, many antibiotics come from natural sources. Penicillin, the first to be synthesised, famously comes from Fleming’s surreptitious mould. These natural antibiotics evolved to keep bacteria at bay between 40 million and 2 billion years ago, so it’s extremely likely that bacteria have been resisting them for just as long.

Second, we know that the environment is teeming with resistance genes. In her own earlier study, D’Costa found that soil bacteria are a massive reservoir for resistance genes – a “resistome “ – which infectious bacteria could draw upon. Meanwhile, Gautam Dantas found that our soils are so full of resistant bacteria that random sampling produced strains that not only resist antibiotics, but actually eat them. He also found that the bacteria in our guts are another reservoir of resistance.

Regardless, D’Costa and King’s point stands: they have certainly found the oldest known examples of resistance genes. There have been similar claims in the past, but all of them controversial. Bacteria are so omnipresent that any team claiming to have found ancient samples must bend over backwards to prove that these aren’t modern contaminants. And none of the previous groups did this well enough, which means that their claims have not been replicated.

To show that their samples are authentically ancient, D’Costa and King pulled out all the stops. They did all of their lab work in special clean rooms. They showed that their samples included DNA from other animals that lived at the right time, such as mammoths, but nothing from species that are common today, like elk, moose or spruce. They even sprayed their drilling equipment, and the surface of their unearthed ice cores, with glow-in-the-dark bacteria. This way, they could immediately tell if anything from the outside world had leached into the interior parts of the cores – the parts where they drew their samples from. Nothing had.

So what does this mean for the problem of antibiotic resistance today? Is this an old problem that is being blown out of proportion? Can we let the wanton use of antibiotics in modern healthcare and agriculture off the hook? Hardly. These conditions still create intense evolutionary pressures that favour the rise of resistant bacteria. The fact that resistant genes are widespread and ancient does not change that. It simply means that in times of need, beleaguered bacteria have a vast and longstanding range of defences to draw from. For every new sword that we fashion, there is a millennia-old shield lying around, just waiting to be brandished again.

Reference: D’Costa, King, Kalan, Morar, Sung, Schwarz, Froese, Zazul, Calmel, Debruyne, Golding, Poinar & Wright. 2011. Antibiotic resistance is ancient http://dx.doi.org/10.1038/nature10388

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