Credit: ZaldyImg. CC BY 2.0.
Credit: ZaldyImg. CC BY 2.0.

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.

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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