When the bacteria that cause anthrax (Bacillus anthracis) aren't ravaging livestock or being used in acts of bioterrorism, they spend their lives as dormant spores. In these inert but hardy forms, the bacteria can weather tough environmental conditions while lying in wait for their next host. This is the standard explanation for what B.anthracis does between infections, and it's too simple by far. It turns out that the bacterium has a far more interesting secret life involving two unusual partners - viruses and earthworms.
A dying animal can release up to a billion bacterial cells in every single millilitre of blood. This torrent of microbes provides a feast of riches for bacteriophages - viruses that infect bacteria. Raymond Schuch and Vincent Fischetti from the Rockefeller University have found that the anthrax bacterium depends on becoming infected by phages. They began by isolating several strains of phages that specifically infect B.anthracis. The viruses hailed from a range of sources, including the soil, plant roots and worm guts. <
When these phages find bacterial targets, they inject their own DNA, which insinuates itself into the genome of the host. This process is called lysogeny and it is essential for the bacterium's survival. The added viral DNA encodes proteins called sigma factors that change how bacterial genes are switched on. In doing so, they change the behaviour of the bacteria, giving them new abilities that boost their survival and allow them to colonise an intermediate host - the earthworm.
With their newly incorporated viral DNA, some bacteria formed spores while others were actually prevented from doing so, depending on the phage. Regardless, all the anthrax bacteria grew at almost twice the rate. The phage DNA brought out the social side of the bacteria, inducing them to cluster in groups. It also made them more likely to secreted more complex sugar molecules that form the building blocks of biofilms - the bacterial equivalent of towns and cities. Amid this matrix of sugars, the cells find shelter and protection.
Small wonder then that the infected bacteria are much better are surviving for long durations. Their advantage was so great in comparison to virus-free strains that Schuch and Fischetti suggest that phage infections may actually be necessary if anthrax bacteria are to survive in soil. Indeed, duo identified three bacterial genes that are activated by the phages and that are necessary for eking out a living in soil. When they inactivated these genes, the bacteria survived in these environments for the briefest of times.
The bacteria don't have to survive in isolation either. Schuch and Fischetti speculate that their biofilms act as a staging ground from which to find a new host. Again, their viral hitchhikers come into play, giving them the ability to set up long-term colonies in the guts of earthworms. That's hardly an easy environment, for it's extremely low in oxygen and most bacteria are digested or excreted. Any permanent hangers-on must be able to stick tightly to the walls of the gut. The genetic manipulations of the virus could activate some latent ability of the bacteria to do just that.
The idea of worms as alternative hosts for anthrax bacteria, in between their decimations of livestock, was first put forward by Louis Pasteur in the 19th century, after he noticed that the soil near anthrax carcasses were rife with earthworms. Ignored for over a century, Pasteur's idea has finally been confirmed.
The viruses within the bacteria aren't totally dormant. Within a small proportion of cells, they multiply as viruses typically do, bursting out of their host and shedding thousands of infectious daughter virses into the environment. This process may kill a few of the anthrax bacteria, but it provides a route for the survivors to trade genetic material between each other.
As phage DNA hops in and out of bacterial genomes, they could take snippets of local DNA with them, transferring them from host to host and increasing the genetic diversity of the population. Don't underestimate how extreme these changes can be: in a previous study, Jonathan Kiel showed that a phage taken from a related species, Bacillus cereus, managed to change a strain of anthrax bacteria so greatly that it was no longer genetically recognisable as the original strain, or even as the right species!
The picture painted by this new study is a far cry from the somewhat dull idea of anthrax bacteria lying dormant in the soil. Instead, it seems that the bacteria lead a secret life, and a most dynamic one, involving hidden potential unleashed by bacterial invaders-turned-partners.
Reference: Schuch, R., & Fischetti, V. (2009). The Secret Life of the Anthrax Agent Bacillus anthracis: Bacteriophage-Mediated Ecological Adaptations PLoS ONE, 4 (8) DOI: 10.1371/journal.pone.0006532
Images: Cow by Daniel Schwen
More on anthrax and phages:
- Wasps use genes stolen from ancient viruses to make biological weapons
- Neutralising anthrax by gumming up a molecular lock
- The virophage - a virus that infects other viruses
It seems to me this should lead us toward suspicion of the independence of phages, and to consider them as organelles or tools of the bacteria. I.e., where did the phages come from in the first place? Is being independently equipped with all the genes for reproduction necessary for this role? Are all phages indeed so equipped? Has anyone checked?
We might view the soil viruses collectively as a genetic library for the bacteria, preserving and providing on demand the technology to thrive in each micro-environment. The bacterium, then, need only carry around a base genome, and pick up what it needs where it lands. Farm animals might represent an unusual low-phage-density, but uniform, environment for which they must -- but can afford to -- carry a specialized genome. The soil, by contrast, is very complex and varied, but the genes needed to survive in each bit can be left behind, packaged as phages, to be picked up as needed.
Or maybe B. a. also draws upon a library of infectiousness-encoding phages it finds in animals' guts.
It's an easy step from book of useful genes to virus. I wonder whether most things that look like phages really are, technically, viruses at all. To test this: do B. anthracis carry any genes whose sole use is to reproduce these phages? If so, that's the smoking gun; if not, we need some other test.
Or maybe the whole virus world originated as "packages of genes left behind".
Trond: Exactly! But the question has been, how do you demonstrate it?
Wasps inject particles that are physically identical to viruses, but lack the genes to code themselves. It seems clear that they started out as a proper virus, because the genes that code it are bunched up on one wasp chromosome. Finding equivalent phage particles would be suggestive, but not conclusive. Suggestions for what else might constitute a proper test, anyone?
Woah ... a virus that's a symbiote? I knew about the wasp that uses a domesticated retrovirus, but this is really cool.
Even the viruses that destroy their host, it seems, would still function as a symbiotic relationship, given that the bacteria reproduce asexually, and thus, it's really more of a situation where the bacterial colony gives some of its members to the viruses?
Very intriguing stuff! I wonder how many more such viral symbiotes there are?
But it seems to me that if this is the case, then the original phage production would have to have been an altruistic act - phages left behind by one bacterium can infect and confer benefit to bacteria that do not produce the phages themselves. So what would have been the selective advantage that drove the evolution of this "proto-phage" production in the first place?
I've been thinking of this since my last post, too. Not good, since I obviously don't know what I'm talking about, but:
Nathan: Exactly! But the question has been, how do you demonstrate it?
By systematic work with the genetic tree of viruses? Might it, in spite of the constant mutations, be feasible to identify one or more core elements that show little change? In that case one might try to identify what part of bacterial (or other) DNA it originally belonged to and find a plausible benefit from leaving that behind for later.
amphiox: So what would have been the selective advantage that drove the evolution of this "proto-phage" production in the first place?
- A cyclic change of conditions.
- String(s) of DNA useful in one environment and harmful in the other.
- A good chance to retrieve the DNA when environment changes back.
The cyclic change could be between an host organism and soil, like for the anthrax bacteria, but this would perhaps have had to be initiated with a stationary host. It could also be a chemical environment with seasons and weather, say water based or dry, again like anthrax, or oxygene based and sulphur based.
amphiox: Excellent question. But the entire population of a parthenogenetically reproducing organism is, in an evolutionarily meaningful sense, really all one organism, just dispersed in space. (In slime molds they even come back together; and how is a bacterial film different from a body?) Your gut is doing equally altruistic stuff on behalf of, well, your gonads, I suppose. But the bacteria are all gonads, so they're all selectively motivated to help one another, to the extent that they can.
The genes they stuff into the viruses -- or that succeed in getting themselves stuffed inthere, as the case may be -- are on their own, but certainly stand to benefit from usefulness, whether they end up in a copy of the mother bacterium or in somebody else entirely. However, they're much more likely to propagate in the former. It's a dilemma: infect a stranger now, and maybe die, or infect mom later, maybe never. Anyway usefulness is selected for in phages in a way that would never occur in viruses that infect us.
Somebody must have thought all this through before. I would love to know where it's all written down.
Great discussion folks. And if you like phages, and their alliances with bacteria, I've got a great story for you later on in the week...