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Cholera Bacteria Kill Each Other With Spears To Steal DNA

The Highlander film series is about a race of immortal warriors who try to behead each other with swords, so they can steal the powers of their fallen rivals.

This is basically the same story but instead of badly accented Scotsmen with katanas, we have diarrhoea-causing bacteria with syringes. And the stolen powers, rather than moving into victors via weird blue lightning, shuffle across as DNA.

The protagonist of this story is Vibrio cholerae. It’s a comma-shaped bacterium with a whip-like tail. We know it best as the cause of cholera—a disease that spreads through contaminated water, and that makes people lose water through both ends. But V.cholerae is only an unfortunate passer-by in drinking supplies and human guts. Its true home is the ocean. There, it hitchhikes on small crustaceans by latching itself to the chitin in their shells.

Chitin changes V.cholerae in important ways. In its presence, the bacteria start making enzymes that can absorb DNA from the environment, including that left behind by other dead and decaying microbes. The bacteria can then integrate the scavenged genes into their own genomes. This new material might allow them to resist antibiotics or infect their hosts more effectively. In other words, the microbes can adapt to new challenges more quickly by sucking up the genetic flotsam left by other bacteria that already had the right adaptations.

This process is called “natural competence for transformation”. It basically means “stealing the powers of your peers”.

But V.cholerae isn’t just a scavenger, waiting to suck up any DNA that happens to floats past. Instead, Sandrine Borgeaud from the Swiss Federal Institute of Technology in Lausanne has shown that it actively kills its neighbours to release their genes, which it can then absorb. It’s a predator. Worse, it’s a cannibal.

Borgeaud initially focused on TfoX—a master gene that is activated in the presence of chitin, and allows V.cholerae to absorb external DNA. To find out how the master dishes out its order, she identified a list of genes that are controlled by TfoX—and found something surprising.

TfoX switches on three clusters of genes that collectively build a fearsome weapon, which bacteria use to stab their competitors. It’s called a “Type Six Secretion System (T6SS)” and consists of 13 separate components. There’s a sheath that contracts to violently ram a tube straight through the outer membrane of another cell. The tube then dispenses proteins that kill and rupture the target.

Type Six Secretion System. It’s a truly dull name for something that’s a cross between a spear-gun and a syringe.

Borgeaud’s team found that V.cholerae can use this weapon to kill other bacteria, including the gut microbe E.coli and even other strains of V.cholerae. They behave like predators that prey upon their own kind. But they don’t kill for nothing. When their prey cells burst open, they release DNA, and the predators can absorb this DNA and whatever adaptive genes it might contain.

Borgeaud confirmed that this happens by unleashing predatory strains of V.cholerae, wielding T6SS spears, upon harmless prey strains. The predators could resist the antibiotic rifampicin, and the prey could resist a different antibiotic—kanamycin. After mixing the two groups of bacteria, Borgeaud exposed them to both antibiotics. By right, every cell should have succumbed to one or either drug. But instead, some of the predators survived and grew because they had absorbed kanamycin-resistance genes from their prey.

The team even developed a way of watching these kills. These time-lapse shots depict one such massacre in progress. The predatory bacteria are dressed in red, and their prey are wearing green. Any time you see a red and a green cell next to each other, the green one is in trouble. As the minutes tick by, the green cells start contracting from commas into full stops, until they eventually burst and die.

Predatory Vibrio cholerae (red) killing prey cells (green). Credit: Borgreaud et al, 2014.
Predatory Vibrio cholerae (red) killing prey cells (green). Credit: Borgreaud et al, 2014.

If you look closely, you can even see the predators feasting on their remains. Borgeaud painted the predators by attaching a glowing red molecule to a protein called ComEA, which they use to smuggle DNA into themselves. ComEA is normally spread throughout its host cell, but it gathers at specific points when its services are required. And you can see that happening in the images above. Focus on the cell with the yellow arrow, and notice how its red glow concentrates into two sharp dots. That’s ComEA gathering. That’s the predator sucking up the remains of its prey.

This discovery is the latest in a long line of research that dates back to the 1920s, when scientists first noticed that harmless strains of bacteria could suddenly start causing disease after mingling with the pulped remains of infectious strains. Something in the extracts was changing these microbes. In 1943, a “quiet revolutionary” named Oswald Avery showed that this transformative material was DNA, which the non-infectious strains had absorbed and integrated into their own genomes.

Matthew Cobb, a zoologist and science historian, describes Avery’s result as “one of the most important discoveries in the history of science” because it suggested, against conventional wisdom, that DNA (and not proteins) was the stuff of genes. He set the groundwork for later discoveries that would cement DNA’s status as the all-important molecule of life—including this new one, which paints DNA as a resource that bacteria will kill for.

Reference: Borgeaud, Metzger, Scrignari & Blokesch. 2014. The type VI secretion system of Vibrio cholerae fosters horizontal gene transfer. http://dx.doi.org/10.1126/science.1260064

6 thoughts on “Cholera Bacteria Kill Each Other With Spears To Steal DNA

  1. Don’t forget that DNA serves primarily as food. Bacteria can always use the nucleotides, but the odds of getting a beneficial gene are very small, probably smaller than the odds of getting a harmful one.

    [Good point, Rosie. Thanks – Ed]

  2. I was wondering about that — how the absorbers of DNA could know which was beneficial, which harmful, which neutral (or just food). Presumably they can’t except by trying them out. Indeed, DNA in the detritus of dead calls might be said to be surrounded by evidence of its inadequacy. One would expect most of the captured DNA to not be of much use as DNA. Yet this elaborate mechanism of attack evolved, so it must have enhanced the survival and reproduction of the predators who use it. Either the predators must have some non-fatal way of evaluating the DNA as DNA, or they’re just eating. The former is a rather interesting concept — could a mere cell do it, and how?

  3. It could be both. The 3 main hypotheses to explain DNA uptake by natural transformation are DNA for food, DNA for variability, and DNA for repair. In the case of Streptococcus pneumoniae in the Oswald Avery experiment, it is now clear that the uptake of DNA is both for repairing damaged DNA in case of stress, and to gain genetic variability. In the case of Vibrio Cholerae, since the bacteria are predating on other species, the DNA for food and/or DNA for variability seem the most probable reasons.
    For how the bacteria can sort out useful genes from harmful ones, I see some possibilities : crispr-cas systems (bacterial adaptive immunity), the difference in GC content of the captured DNA, the need for some homology to allow recombination in the predator chromosome…
    A great review on the topic : Johnston et al., Nat rev micro 2014

  4. There’s a sheath that contracts to violently ram a tube straight through the outer membrane of another cell. The tube then dispenses proteins that kill and rupture the target.

    This horizontal gene transfer sounds a little like copulation. I can’t help but think it has the potential to evolve into a reproductive system. Genes that could get themselves into those proteins might have a shot at replicating in a new host that has immune defense against digestion.

    [Bacteria do swap genes through a different mechanism called conjugation, which is very much like copulation. They actually form physical bridges between their cells and shunt DNA across. – Ed]

  5. I just try (and fail) to understand how this might have evolved. The “interested” part of the bacteria (both sides) *is* the DNA. The red cell’s DNA just takes a risk by inviting a competitor into its cell. OTOH the green cell’s DNA might be interested to invade the red cell, but then the green cell should be the attacking one (such mechanisms do exist among bacteria, but the phenomenon described here is just the opposite).

  6. Ralf Muschall, it seem to me that such a system could readily evolve if the first and primary advantage is using the capture DNA as food, as a source of ready-made nucleotides and deoxyribose sugars. Other materials from the lysed victim cells, like proteins, can also be used as food, and just killing neighbouring cells that compete with you can also be beneficial.

    So the T6SS can first evolve as a general purpose weapon and the uptake of the new DNA can have first evolved for using the DNA as food.

    The integration of DNA in the genome can subsequently have evolved by a number of possible mechanisms:

    1) it may have already existed as part of a bacterial conjugation system that integrates foreign DNA into the genome. The system would treat all available DNA the same regardless of how it got into the cell, whether through bacterial sex/conjugation or by predatory behavior.

    2) it could have started as an incidental side effect of feeding on DNA for food, in that the process of digesting the captured DNA would produce random chunks of DNA, some of which would inevitably get recombined into the genome in the process of normal DNA replication and repair. If this random side effect produces beneficial outcomes some of the time, that would be enough for natural selection to hone the process.

    3) part of it could have evolved as a defence mechanism for the victim DNA (ie it is the victim DNA that is doing the evolving). The victim DNA may evolve sequences that resist digestion by the predator trying to chew it up for food, and promote its chances of being integrated into the predators genome, so it can survive in a new host. And since it then becomes in the interest of this DNA for its new host to survive, natural selection would favor DNA that is capable of conferring advantages to the new host.

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