Mud time capsules show evolutionary arms race between host and parasite

Evolution can sometimes be seen as a futile contest. Throughout the natural world, pairs of species are locked in an evolutionary arms race where both competitors must continuously evolve new adaptations just to avoid ceding ground. Any advantage is temporary as every adaptive move from a predator or parasite is quickly neutralised by a counter-move from its prey or host. Coerced onward by the indifferent force of natural selection, neither side can withdraw from the stalemate.

These patterns of evolution are known as Red Queen dynamics, after the character in Lewis Carroll’s Through the Looking Glass who said to Alice, “It takes all the running you can do, to keep in the same place.”

These arms races are predicted by evolutionary theory, not least as an explanation for sex. By shuffling genes from a mother and father, sex acts as a crucible for genetic diversity, providing a species with the raw material for adapting to its parasites and keep up with the arms race.

Watching the race

We can see the results of Red Queen dynamics in the bodies, genes and behaviours of the species around us but actually watching them at work is another matter altogether. You’d need to study interacting species over several generations and most biologists have neither the patience nor lifespan to do so.

But sometimes, players from generations past leave behind records of the moves they made. Ellen Decaestecker and colleagues from Leuven University found just such an archive in the mud of a Belgian lake.

MRSA gets piggyback from livestock to humans

I’ve written an article for the Economist about a new strain of the antibiotic-resistant “superbug” MRSA (methicillin-resistant Staphylococcus aureus) that infects large numbers of farm pigs and can jump into humans.

The strain was first found in pig farms in the Netherlands and may be picking up new resistances from their porcine hosts because of the large amounts of antibiotics used to medicate livestock.

The piece is in the Science and Technology section of the November 29th issue of the Economist (out in the UK tomorrow) but you can already read it online. I’m pretty excited about this – it’s certainly the most prestigious magazine I’ve had the opportunity to write for.

Cooperating bacteria are vulnerable to slackers

As a species, we hate cheaters. Just last month, I blogged about our innate desire to punish unfair play but it’s a sad fact that cheaters are universal. Any attempt to cooperate for a common good creates windows of opportunity for slackers. Even bacteria colonies have their own layabouts. Recently, two new studies have found that some bacteria reap the benefits of communal living while contributing nothing in return.

Bacteria may not strike you as expert co-operators but at high concentrations, they pull together to build microscopic ‘cities’ called biofilms, where millions of individuals live among a slimy framework that they themselves secrete. These communities provide protection from antibiotics, among other benefits, and they require cooperation to build.

This only happens once a colony reaches a certain size. One individual can’t build a biofilm on its own so it pays for a colony to be able to measure its own size. To do this, they use a method ‘quorum sensing’, where individuals send out signalling molecules in the presence of their own kind.

When another bacterium receives this signal, it sends out some of its own, so that once a population reaches a certain density, it sets off a chain reaction of communication that floods the area with chemical messages.

These messages provide orders that tell the bacteria to secrete a wide range of proteins and chemicals. Some are necessary for building biofilms, others allow them to infect hosts, others make their movements easier and yet others break down potential sources of food. They tell bacteria to start behaving cooperatively and also when it’s worth doing so.

Space flight turns Salmonella into super-bug

Science fiction loves to play off the potential threat of threat of alien viruses. But a new study suggests that space travellers are much more likely to be threatened by germs from our own planet that become more virulent in space.

Warding off infections is a real priority for astronauts, especially if longer space missions to the Moon and Mars are to go ahead. People have a tendency to get sick in space and over half of the astronauts on the Apollo missions became ill during their trips or soon after their return to Earth.

Earlier research has shown that prolonged weightlessness weakens our immune systems by preventing key sets of genes from switching on. But that’s only part of the problem. A team of researchers from NASA, Arizona State University and 12 other institutions has shown that bacteria also react to zero-gravity conditions, by becoming more virulent, or able to cause disease.

An entire bacterial genome discovered inside that of a fruit fly

Bacteria have the ability to transfer genes to one another. Now, scientists have found that one species, Wolbachia, has managed to transfer its entire genome into that of a fruit fly. These extreme gene transfers could be more common than we thought, and they have important consequences for genome-sequencing projects.

A humble species of fruit fly is the genetic equivalent of a Russian doll – peer inside its DNA and you will see the entire genome of a species of bacteria hidden within.

The bacteria in question is Wolbachia, the most successful parasite on earth and infects about 20% of the world’s species of insects. It’s a poster child for selfishness. To further its own dynasty, it has evolved a series of remarkable techniques for ensuring that it gets passed on from host to host. Sometimes it gives infected individuals the ability to reproduce asexually; at other times, it does away with an entire gender.

Now, Julie Dunning-Hotopp from the J. Craig Venter Institute and Michael Clark from the University of Rochester have found an even more drastic strategy used by Wolbachia to preserve its own immortality – inserting its entire genome wholesale into that of another living thing.

The secret of drug-resistant bubonic plague

The bacterium that causes bubonic plague can pick up drug resistance from common bacteria responsible for food poisoning.

The plague, or the Black Death, is caused by a microbe called Yersinia pestis (right). In the 14^th century, this microscopic enemy killed off a third of Europe’s population.

While many people consign the plague to centuries past, this attitude is a complacent one. Outbreaks have happened in Asia and Africa over the last decade and the plague is now recognised as a re-emerging disease.

In 1996, two drug-resistant strains of plague were isolated from Madagascar. One of these, was completely resistant to all the drugs that are used to control outbreaks.

Any scientist currently studying tuberculosis can attest to the ability of bacteria to evolve resistance to drugs. In the case of drug-resistant plague, the secret to its powers is a plasmid – a small free-floating ring of DNA, that carries drug resistance genes.

Bacteria can trade plasmids across individuals, transferring genes between each other in ways that humans can only achieve with technology.

The worry is that common and less harmful bacteria could transfer drug-resistance plasmids over to Yersinia, resulting in new resistant strains.

Timothy Welch and colleagues from the United States Department of Agriculture showed that this concern is well-founded. They found that the plague plasmid is virtually identical in parts to plasmids from an increasingly common strain of Salmonella (left) that is also resistant to multiple drugs.

They even found related plasmids were in other drug-resistant bacteria isolated from meat samples across the USA during quality control checks.

A word of caution – this doesn’t mean that people risk contracting plague from eating meat. Even though the plasmids are strikingly similar, the bacteria involved are very different.

But it does mean that the plague bacterium could potentially gain drug resistance from other common resistant bacteria, if they should both find themselves in the same human or flea host.

Despite this scary scenario, Welch’s study also provides us with a silver lining. We are aware of the threat and we know how to monitor for it, by searching for the plasmid.

Monitoring is especially important because the plague has all the qualities you would look for in a potential biological weapon – a high fatality rate, no vaccine and possible air-borne transmission.

If the worst happens, we will want to be prepared.

 

Reference: Welch, Fricke, McDermott, White, Rosso, Rasko, Mammel, Eppinger, Rosovitz, Wagner, Rahalison, LeClerc, Hinshaw, Lindler, Cebula, Carniel& Ravel. 2007. Multiple antimicrobial resistance in plague: an emerging public health risk. PLOS ONE.

Technorati Tags: bubonic plague, plague, black death, Yersinia, drug resistant, science,

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Human gut bacteria linked to obesity

The obesity epidemic is a massive concern for the 21st century. New research shows that the bacteria that live inside our digestive systems could have a large impact on our risk of being obese.

There is a widespread belief, that being overweight or obese is a question of failing willpower, fuelled in no small part by food, fitness and beauty industries. But if we look at the issue of obesity through a scientific spyglass, a very different picture emerges.

Research is increasingly showing that a large part of the tendency to become obese is genetically controlled, often in very subtle ways. Genetic variation could mean that some people are more sensitive to the smell or sight of food, or are less able to sense when they are full. These small variations can play havoc in our modern environment, where calories are readily available and inactive lifestyles are common.

But it’s not just our own genes that we should be worried about. In terms of processing food, humans are hardly self-sufficient. Our guts are the home of trillions of bacteria that help to break down foodstuffs that our own cells cannot cope with. Together the genes expressed by these intestinal comrades outnumber our own by thousands of times, and yet we are still largely in the dark what they do.

Over 90% of these bacteria, collectively known as the microbiota, come from just two groups – the Bacteroidetes and the Firmicutes. Now, new research suggests that the proportion of these groups is an important factor in the obesity epidemic.

Ruth Ley, Peter Turnbaugh, Jeffrey Gordon and colleagues at Washington University first noticed the link between the microbiota and obesity by studying a special strain of fat mice.

These mice lack the hormone leptin, which controls the body’s ‘fat thermostat’. Without it, the mice cannot monitor the amount of fat in their body and quickly become obese through overeating. The team noticed that these mice had 50% fewer Bacteroidetes and 50% more Firmicutes in their bowels than their lean counterparts.

They saw the same thing in humans. The relative proportion of Bacteroidetes increased in obese people as they lost weight through low-fat or low-carbohydrate diets, while the Firmicutes became less abundant.

The link between the microbiota and obesity became even clearer when Gordon looked at a special strain of mice with no microbiota of their own. These intestinal tabula rasas proved to be strongly resistant to the fattening effects of unhealthy diets. After eight weeks on a 40% fat diet, these animals put on less than half as much weight as their normal peers, despite eating the same amount of food.

When the team transplanted the microbiota from fat and lean mice into the germ-free strains, those colonised by microbiota from fat donors packed on far more weight than those paired with lean donors.

To find out why the shifting bacterial balances were affecting body weight, Gordon and co. compared the microbiota of fat and lean mice at a genetic level. Samples from fat mice showed much stronger activation of genes that coded for carbohydrate-destroying enzymes, which break down otherwise indigestible starches and sugars. As a result, these mice were extracting more energy from their food than their lean cousins.

The bacteria were also manipulating the animals’ own genes, triggering biochemical pathways that store fats in the liver and muscles, rather than metabolising them. While these effects are relatively small, Gordon believes that they can lead to very large fluctuations in weight, over the course of months or years.

Obviously, the microbiota are not the whole story behind the obesity epidemic. We now need to understand how they interact with other things that affect our risk of becoming obese, not least of all, our own genes.

And there is much we still don’t know about our life-long passenger, such as how they sense and respond to their host’s condition, how they are passed on, or how they are affected by our diet. By answering these questions, scientists could then assess whether actively shifting our bacterial balances could help to stem the worldwide increase in obesity levels.

Backhed, Manchester, Semenkovich & Gordon. 2006. PNAS 104: 979-984.
Ley, Turnbaugh, Klein & Gordon. 2006. Nature 444: 1022-1023. Turnbaugh, Ley, Mahowald, Magrini, Mardis & Gordon. 2006. Nature 444: 1027-1031.
Technorati Tags: obesity, bacteria, gut bacteria, intestinal flora, Bacteroidetes, Firmicutes, microbiota, causes of obesity, science

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Too few genes to survive – a bacteria with the world’s smallest genome

The complex cells that make up plants and animals only survive today because their ancestors formed partnerships with bacteria. A previous article in this blog discusses the first steps in this partnership. Now, scientists have discovered a bacterium that embodies one of the later stages, having lost so many genes that it cannot possibly survive outside of its host.

In a previous article, I described how a micro-organism called Hatena provides us with a snapshot of a key event in evolution. Hatena swallows an alga which becomes an integrated part of its body. Millions of years ago, the ancestors of complex cells did the same thing, taking in bacteria and merging with them to form a single creature.

Today, these integrated bacteria are mitochondria (right), which provide us with energy, and chloroplasts, which allow plants to photosynthesise.

Hatena and its algal partner show us what the first step in this process was like. Now, another group of scientists have found a species of bacteria – Carsonella ruddii – that illustrates the next stage, the exchange of genes.

Typically, the lodger would shunt some of its genetic material over to its host. It has permanent room and board and can afford to rid itself of excess genetic baggage that was once necessary for its free-living existence.

Carsonella lives in the bodies of sap-sucking insects and provides them with nutrients lacking in their diet. Atsushi Nakabachi and co-workers from the RIKEN Institute in Japan found that Carsonella is minute, packing its entire complement of genes into just 160,000 base pairs.

Previously, scientists had assumed that bacteria need genomes of at least 400,000 base pairs to survive. Any less, and they wouldn’t be able to carry out even the most basic of biological functions. And indeed, Carsonella cannot. Many of the genes that are essential to normal bacteria have vanished.

Of the remaining few, half are devoted to the most basic of all cellular processes – dealing with amino acids, and building them into proteins. Plant sap is poor in some essential amino acids, so most likely, these genes are still there to serve the host insect, not the bacterium itself.

Not only has Carsonella pared its genes down to the bare essentials, it has also arranged with remarkable efficiency. Nine in ten of its genes overlap with each other, and they cover 97% of its genome. In contrast, humans are much more lackadaisical with our packaging and about 98% of our genomes is made up of so-called ‘junk DNA’.

The result of this genetic streamlining is an organism that is completely incapable of living on its own. Carsonella is well down the evolutionary path towards becoming an essential part of its host cell, completey devoid of independence. It provides strong support for the idea that modern mitochondria and chloroplasts evolved in the same way.

These essential components of today’s cells have their own massively reduced genomes, and most of the genes they need are stored and deployed by the host. While they have abandoned their independence, they are just as essential for their host as their hosts are to them.

Nakabachi, Yamashita, Toh, Ishikawa, Dunbar, Moran & Hattori. 2006. Science 314: 267.

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Neutralising anthrax – moving closer to a cure

Since the anthrax postal attacks of 2001, the race has been on to find new ways of treating the disease. Now, scientists have developed a treatment that completely neutralises anthrax toxins, by acting on the host’s own cells rather than the bacteria itself.

 

In the final months of 2001, five people died because they opened their mail. The killers were hidden inside the envelopes, small spores that were inhaled by the unfortunate addresses. Inside their bodies, the spores turned into the deadly bacteria, Bacillus anthracis – anthrax (right).

Anthrax has a long history in biological warfare but it made its debut as an agent of bioterror in 2001. The US anthrax postal attacks infected 22 people and claimed the lives of five. Since then, scientists have been feverishly studying anthrax in the hope that better understanding will lead to effective treatments.

We now know that a protein called PA acts as a figurate and literal key to anthrax’s infiltration of mammalian cells. PA fits into molecular locks on host cells, known as anthrax receptor 1 and 2 (ANTXR1 & ANTXR2). When this happens, PA is unwittingly taken into the host cell where it creates its own doorway in the cell’s membrane. This secret passage allows the virus to send in more dangerous and toxic agents like the sinisterly named lethal factor (LF).

Several researchers have tried to develop anti-anthrax measures by destroying or blocking the key protein, PA, but these solutions face a large problem. Bacteria already have a good track record for developing resistance to treatments. And since anthrax is a potential biological weapon, it may well be intentionally re-engineered to fool any counter-measures used to stop it.

We need a different line of defence, and Saleem Basha and Prakash Rai at the Rensselaer Polytechnic Institute, New York, have found one – if you can’t destroy the key, stick gum in the lock.

To find a suitable piece of gum, the duo started off with a random collection of peptides – short chunks of protein. They exposed this collection to ANTXR1 and 2, in the hope that some of them would have the right shape to latch onto these locks. Any peptides without this X-factor were washed off. Basha and Raj repeated this process several times so that only those peptides that stuck very strongly to the anthrax receptors remained.

Once they had homed in on their star peptide, they decided to go for strength in numbers. They attached multiple copies of the peptide of choice to a molecular scaffold, allowing it to gang up on any threatening virus. In laboratory tests, these scaffolds increased the peptide’s efficiency by over 50,000 times.

Having proved its worth in the lab, the researchers gave their anti-anthrax peptide a field test. They injected six rats that with anthrax toxin and their peptide scaffold and amazingly, all six showed no signs of infection or ill health. By sticking to ANTXR1 and 2, the peptide prevented PA from getting a foothold, leaving it knocking on the door in vain. It completely neutralised the anthrax toxins.

Currently, antibiotics do nothing for anthrax patients once symptoms have developed. They can rid people of the bacteria but do nothing to stop the toxins already in the body from wreaking further havoc. The peptide on the other hand can do that, and could provide the breakthrough needed to effectively treat patients.

Basha and Raj’s method also has many applications for designing ways of fighting other diseases. Bacteria often acquire resistance to treatments and antibiotics, leading to new threats like drug-resistant tuberculosis, and the infamous MRSA bug. But Basha and Raj’s fast and inexpensive technique overcomes the problem of resistance, by ignoring the threat itself and instead cutting off its point of attack.

 

 

Basha, Raj, Poon, Saraph, Gujraty, Go, Sadacharan, Frost, Mogridge & Kane. 2006. PNAS 103: 13509-13513

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