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
More on drug-resistant bacteria
The road of East Smithfield runs through east London and carries a deep legacy of death. Two cemeteries, established in the area in the 14th century, contain hundreds of bodies, piled five deep. These remains belong to people killed by the Black Death, an epidemic that claimed up to 100 million lives. It was one of the biggest disasters in human history and seven centuries on, its victims are still telling its story.
In the latest chapter, Verena Schuenemann from the University of Tubingen and Kirsten Bos from McMaster University have reconstructed parts of the genome of the Black Death plague bacterium, and found features that are unlike any seen today. In line with another study from last year, Schuenemann and Bos’s work suggests that the great butcher of medieval Europe may no longer exist.
From “gut feelings” to “having some guts”, English is full of phrases where our bowels exert an influence upon our behaviour. But these are more than metaphors. There are open lines of communication between brains and bowels and, in mice at least, these channels allow an individual’s gut bacteria to steer their behaviour.
The latest evidence for this “gut-brain axis” comes from Javier Bravo at University College Cork. He fed mice with a probiotic bacterium called Lactobacillus rhamnosus, often found in yoghurts and dairy products. The bacterial menu changed the levels of signalling chemicals in the rodents’ brains, and reduced behaviours associated with stress, anxiety and depression.
Probiotic bacteria – those that benefit their host – are the subject of sweeping, hand-waving health claims. But beneath the breathless marketing hype, there is some intriguing underlying science. For example, some trials have found that probiotics can help to alleviate the mood symptoms that accompany irritable bowel or chronic fatigue syndrome. To that end, Bravo wanted to see if L.rhamnosus could influence the brains of normal, healthy animals.
Stem cells are bursting with potential. They can produce every type of cell in the human body. Small clumps of them can generate entire individuals. But this ability, known as pluripotency, is hard won. So stem cells must constantly repress genetic programmes that threaten to send them down specific routes, and rob them of their limitless potential. “Imagine you’re a stem cell,” says Mitchell Guttman from the Broad Institute of MIT and Harvard. “The worst thing that could happen is that you accidentally turn on, say, neural genes and become a brain cell.”
Now, Guttman has found that stem cells keep themselves ‘stemmy’ with a group of genes called lincRNAs. His discovery not only assigns an important role to these mysterious genes, it opens up a new potential way of precisely controlling what goes on inside a cell.
The Neanderthals may be extinct, but they live on inside us. Last year, two landmark studies from Svante Paabo and David Reich showed that everyone outside of Africa can trace 1-4 percent of their genomes to Neanderthal ancestors. On top of that, people from the Pacific Islands of Melanesia owe 5-7 percent of their genomes to another group of extinct humans – the Denisovans, known only from a finger bone and a tooth. These ancient groups stand among our ancestors, their legacy embedded in our DNA.
Paabo and Reich’s studies clearly showed that early modern humans must have bred with other ancient groups as they left Africa and swept around the world. But while they proved that Neanderthal and Denisovan genes are still around, they said little about what these genes are doing. Are they random stowaways or did they bestow important adaptations?
How does an ostrich sleep? Almost imperceptibly, it seems. Even though an ostrich might be sound asleep, it can look wide awake or, at most, a little drowsy. John Lesku from the Max Planck Institute of Ornithology discovered this by fitting six ostrichers with “Neurologgers”, electrode-laden helmets that measures their temperature, brain activity, eye movements and neck muscle contractions.
The video above shows three of the birds cycling through two different types of sleep. The first is called ‘slow wave sleep’ or SWS, where the ostriches’ brain waves are slow and strong. Even though this is typically known as deep sleep, the birds look alert. They stay still, but their eyes are open and their necks upright. Nonetheless, the readings from the Neurologgers clearly showed that they were asleep.
In the second phase, known as ‘rapid eye movement’ or REM sleep, the ostriches’ brain waves are fast and weaker. Now, the birds shut their eyes, which move rapidly behind closed eyelids. They necks also start to droop and sway, righting themselves with awkward jerks like people falling asleep at a talk. Biologists have previously interpreted this as a sign of a tired ostrich. That’s partly right, although the animal is already asleep rather than on its way.
Over the last three years, a group of scientists have been going round two suburbs of Cairns, Australia, and asking local people if they could release mosquitoes on their properties. Ninety percent said yes. These were no ordinary mosquitoes. They had been loaded with bacteria that stop them from passing on the virus that causes dengue fever.
Dengue fever affects thousands of Queenslanders every year. It is caused by an alliance of two parasites – the dengue virus, and the Aedes aegypti mosquito that spreads it. In an ambitious plan to break this partnership, Scott O’Neill from the University of Queensland turned to yet another parasite – a bacterium called Wolbachia. It infects a wide variety of insects and other arthropods, making it possibly the most successful parasite of all. And it has a habit of spreading with great speed.
Wolbachia is transmitted in the eggs of infected females, so it has evolved many strategies for reaching new hosts by screwing over dead-end males. Sometimes it kills them. Sometimes it turns them into females. It also uses a subtler trick called “cytoplasmic incompatibility“, where uninfected females cannot mate successfully with infected males. This means that infected females, who can mate with whomever they like, enjoy a big advantage over uninfected females, who are more restricted. They lay more eggs, which carry more Wolbachia. Once the bacterium gets a foothold in a population, it tends to spread very quickly.
Forty years ago, the elkhorn coral was one of the most common species in the Caribbean. Five years ago, it was listed as critically endangered. The coral’s woes are many but, aside from the warming temperatures, predators and storms that affect all corals, the elkhorn is also plagued by a highly contagious malady called white pox disease. White lesions erupt all over the coral’s branches, representing areas where its animal tissue has wasted away to leave the white skeleton.
Now, Kathryn Patterson Sutherland from Rollins College in Florida has discovered the cause of white pox disease, and it’s an unexpected one – us. We have literally landed the elkhorn in s**t.
Every time you drink a pint of lager, you owe a debt to a small fungus that lives in the beech forests of Patagonia. This previously undescribed species – Saccharomyces eubayanus – merged with a close relative to create a hybrid, whose fermenting abilities produce all of today’s lagers. Without it, our pints would have a much darker complexion.
Ask someone to think of a domesticated species and they’ll probably think of something like a dog, cat, cow or horse. But domesticated fungi are just as close to our hearts or, at least, our livers. The yeast, Saccharomyces cerevisiase, has been used to bake bread and ferment wine or ales for centuries. But it’s only partially involved in lagers.
Lager is fermented at a lower temperature than either ale or wine, and the fungus for the job is a cold-tolerant species called S.pastorianus. It has never been found in the wild, and its genes tell us why. It has four of each chromosome, and appears to be a fusion of two different yeast species. One of these is S.cerevisiae but the identity of the second partner has been a long-running mystery. Until now, the best guess was yet another species of cold-tolerant yeast called S.bayanus. But like S.pastorianus, S.bayanus has never been found in the wild.