Many insects eventually evolve to resist insecticides. This process typically takes many generations and involves tweaks to the insect’s genes. But there is a quicker route. Japanese scientists have found that a bean bug can become instantly resistant to a common insecticide by swallowing the right bacteria.
The bug forms an alliance with Burkholderia bacteria, and can harbour up to 100 million of these microbes in a special organ in its gut (see arrow above). Some strains of Burkholderia can break down the insecticide fenitrothion, detoxifying it into forms that are harmless to insects. In fields where the chemical is sprayed, these pesticide-breaking bacteria rise in number. And if bugs swallow them, they become immune to the otherwise deadly chemical.
I’ve written about this story for The Scientist, so head over there to read the details of the study.
The caverns of Lechuguilla Cave are some of the strangest on the planet. Its acid-carved passages extend for over 120 miles. They’re filled with a wonderland of straws, balloons, plates, stalactites of rust, and chandeliers of crystal.
Parts of Lechuguilla have been cut off from the surface for four to seven million years, and the life-forms there – mainly bacteria and other microbes – have charted their own evolutionary courses. But Gerry Wright from McMaster University in Canada has found that many of these cave bacteria can resist our antibiotics. They have been living underground for as long as modern humans have existed, but they can fend off our most potent weapons. Drug resistance may be causing problems for us now, but for bacteria, it’s just an ancient solution to an ancient problem.
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
Since 1948, people have been poisoning unwanted rats and mice with warfarin, a chemical that causes lethal internal bleeding. It’s still used, but to a lesser extent, for rodents have become increasingly resistant to warfarin ever since the 1960s. This is a common theme – humans create a fatal chemical – a pesticide or an antibiotic – and our targets evolve resistance. But this story has a twist. Ying Song from Rice University, Houston, has found that some house mice picked up the gene for warfarin resistance from a different species.
Warfarin works by acting against vitamin K. This vitamin activates a number of genes that create clots in blood, but it itself has to be activated by a protein called VKORC1. Warfarin stops VKORC1 from doing its job, thereby suppressing vitamin K. The clotting process fails, and bleeds continue to bleed.
Rodents can evolve to shrug off warfarin by tweaking their vkorc1 gene, which encodes the protein of the same name. In European house mice, scientists have found at least 10 different genetic changes (mutations) in vkorc1 that change how susceptible they are to warfarin. But only six of these changes were the house mouse’s own innovations. The other four came from a close relative – the Algerian mouse, which is found throughout northern Africa, Spain, Portugal, and southern France.
The two species separated from each other between 1.5 and 3 million years ago. They rarely meet, but when they do, they can breed with one another. The two species have identifiably different versions of vkorc1. But Song found that virtually all Spanish house mice carry a copy of vkorc1 that partially or totally matches the Algerian mouse version. Even in Germany, where the two species don’t mingle, a third of house mice carried copies of vkorc1 that descended from Algerian peers.
We are losing the war against infectious bacteria. They are becoming increasingly resistant to our antibiotics, and we have few new drugs in the pipeline. Worse still, bacteria can transfer genes between each other with great ease, so if one of them evolves to resist an antibiotic, its neighbours can pick up the same ability. But Matti Jalasvuori from the University of Jyvaskyla doesn’t see this microscopic arms-dealing as a problem. He sees it as a target.
Usually, antibiotic-resistance genes are found on rings of DNA called plasmids, which sit outside a bacterium’s main genome. Bacteria can donate these plasmids to one another, via their version of sex. The plasmids are portable adaptations – by trading them, bacteria can rapidly respond to new threats. But they aren’t without their downsides. Plasmids can sometimes attract viruses.
Bacteriophages (or “phages” for short) are viruses that infect and kill bacteria, and some of them specialise on those that carry plasmids. These bacteria may be able to resist antibiotics, but against the phages, their resistance is futile.
Even bacteria get sick. Tiny though they are, bacteria can be infected by even tinier viruses known as phages. Like tiny hypodermic needles, phages inject their genetic material into their bacterial hosts, turning them into factories for making more phages. The host usually dies in the aftermath. But some bacteria have turned these enemies into their allies. By adding the viruses’ DNA into their own genomes, they have become superbugs, able to tolerate harsh environments and shrug off antibiotics.
Once phages have injected their genes into a bacterium, they can make copies of themselves in two ways. The first is a brutish approach. The genes commandeer the host, using it to manufacture new viruses that eventually burst out of the cell – this is the lytic cycle. Alternatively, the phage DNA can infiltrate the bacterium’s genome, becoming part of it. When the bacterium divides in two, it copies the phage’s genes along well as its own. This is the lysogenic cycle, an altogether stealthier approach to making more phages.
Within the bacterial genome, the viral DNA is called a prophage. After being copied many times over in these new surroundings, it can pop out again to create a new phage. The prophage is little more than a genetic parasite. But sometimes, a prophage gets trapped by a crippling mutation. Unable to pop out, it becomes a genetic fossil, forever stuck within its host and destined only to preserve a trace of a past infection.
Humans are capable of great charity, taking hits to their bank accounts and bodies to benefit their peers. But such acts of altruism aren’t limited to us; they can be found in the simple colonies of bacteria too.
Bacteria are famed for their ability to adapt to our toughest antibiotics. But resistance doesn’t spring up evenly across an entire colony. A new study suggests that a small cadre of hero bacteria are responsible for saving their peers. By shouldering the burden of resistance at a personal cost, these charitable cells ensure that the entire colony survives.
Our bodies are under siege, constantly fighting back assaults from disease-causing bacteria. But we are also home to many harmless bacterial species that are share our bodies to no ill effects. Now, it seems that these ‘commensals’ could be our hidden allies against their harmful cousins. In one such ally, a group of scientists has just discovered a potential new weapon against Staphylococcus aureus.
Methicillin-resistant Staphylococcus aureus (MRSA) is very difficult to kill. This notorious “superbug” can withstand a broad and growing range of antibiotics, and is the leading cause of hospital infections in many countries. But it’s not restricted to hospitals. According to studies coming in from all over the world, MRSA has found a new route into our bodies -piggyback.
Pig farms throughout the world have become breeding grounds for strains of MRSA that can jump from swine to humans. These strains have already been isolated in the Netherlands, Denmark and Canada, and now, the latest study adds the USA to that list. The research was led by Tara Smith from the University of Iowa, who I know as a Scibling and who many of you will recognize as the author of the excellent Aetiology blog.
Smith found widespread traces of MRSA in two different production systems in the states of Iowa and Illinois. Within the nostrils of 49% of pigs and 45% of pig farmers, her team detected traces of the “superbug” (although it’s worth noting that none of the farmers had experienced any actual infections). Piglets had the highest rates of infection and in fact, every single pig under the age of 12 weeks harboured MRSA colonies.
The high levels of the bacterium in both man and pig suggest that it can spread readily between the two species. To MRSA, both four leg and two legs are good…
When normal bacteria are exposed to a drug, those that become resistant gain a huge and obvious advantage. Bacteria are notoriously quick to seize upon such evolutionary advantages and resistant strains rapidly outgrow the normal ones. Drug-resistant bacteria pose an enormous potential threat to public health and their numbers are increasing. MRSA for example, has become a bit of a media darling in Britain’s scare-mongering tabloids. More worryingly, researchers have recently discovered a strain of tuberculosis resistant to all the drugs used to treat the disease.
New antibiotics are difficult to develop and bacteria are quick to evolve, so there is a very real danger of losing the medical arms race against these ‘super-bugs’. Even combinations of drugs won’t do the trick, as resistant strains would still flourish at the expense of non-resistant ones. Antibiotic combos could even speed up the rise of super-bugs by providing a larger incentive for evolving resistance.
Clearly, fighting the rapidly evolving nature of bacteria is a dead end. So Remy Chait, Allison Craney and Roy Kishoni from Harvard Medical School used a different strategy – they changed the battle-ground so that non-resistant bacteria have the advantage. And they have done so using the seemingly daft strategy of using combinations of drugs that work poorly together, and even those that block each other’s effects.