To kill off the competition, bacteria throw pieces of dead viruses at them

Enlarge / This is an intact phage. A tailocin looks like one of these with its head cut off.

Long before humans became interested in killing bacteria, viruses were already at the task. Viruses that attack bacteria, called “phages” (short for bacteriophage), were first identified by their ability to create bare patches on the surface of culture dishes that would otherwise be covered by a layer of bacteria. After playing a pivotal role in the early development of molecular biology, several phages have been developed as potential therapies to be used when antibiotic resistance limits the effectiveness of traditional medicines.

But we are relatively late in terms of turning phages into tools. Researchers have described a number of cases where bacteria have kept deactivated virus fragments in their genomes and turned them into weapons that can be used to kill other bacteria that might otherwise compete for resources. I only recently became aware of this use as a weapon, thanks to a new study that shows that this process has helped maintain diverse bacterial populations for centuries.

Evolving a killer

The new work began when researchers were studying the population of bacteria associated with a plant growing wild in Germany. The population included various members of the genus. Pseudomonas, which may include plant pathogens. Normally, when bacteria infect a new victim, a single strain expands dramatically while successfully exploiting its host. In this case, however, the Pseudomonas The population contained a variety of different strains that appeared to maintain stable competition.

To learn more, the researchers obtained more than 1,500 individual genomes from the bacterial population. More than 99 percent of those genomes contained virus fragments, and the average bacterial strain had two separate virus fragments hidden in its genomes. All of these were missing parts compared to a functional virus, suggesting that they were the product of a virus that had been inserted in the past but had since suffered damage that incapacitated them.

By itself, that’s not surprising. Many genomes (including ours) contain many inactivated viruses. But bacteria tend to remove foreign DNA from their genomes fairly quickly. In this case, a particular viral sequence appeared to trace back to the common ancestor of many of the strains, as they all had the virus inserted into the same genome location, and all instances of this particular virus had been inactivated by losing the viral sequence. same set of genes. The researchers named this sequence VC2.

Many phages have a stereotypical structure: a large “head” containing their genetic material, placed on a stalk that ends in a set of “legs” that help them adhere to their bacterial victims. Once the legs make contact, a stem contracts, an action that helps transfer the virus genome to the bacterial cell. In the case of VC2, all copies lacked the genes to produce the head section, as well as all the genes needed to process its genome during infection.

This made researchers suspect that VC2 was something called “tailocin.” These are ancient phages that have been domesticated by bacteria so that they can be used to harm the bacteria’s potential competition. Bacteria with colacin can produce partial phages consisting only of legs and stem. These tailocins can still find and attach to other bacteria, but when the stem contracts, there is no genome to inject. Instead, this simply opens a hole in its victim’s membrane, partially removing the cell’s boundary and allowing some of its contents to escape, causing its death.

An evolutionary battle against all

To confirm that the VC2 sequence encodes a colacin, the researchers grew some bacteria containing the sequence, purified proteins from it, and used electron microscopy to confirm that they contained headless phages. By exposing other bacteria to tailocin, they found that while the strain that produced it was immune, many other strains growing in the same environment died. When the team deleted the genes that encode key parts of tailocin, the killing disappeared.

The researchers hypothesize that the system is used to eliminate potential competitors, but that many strains have developed resistance to tailocin.

When researchers did a genetic screen to identify resistant mutants, they discovered that the resistance was provided by mutations that interfered with the production of complex sugar molecules found in proteins that end up on the outside of cells. At the same time, most of the genetic differences between the VC2 genes occur in the proteins that the legs encode, which attach to these sugars.

So it appears that each bacterial strain is both an aggressor and a victim, and there is an evolutionary arms race leading to a complex collection of pairwise interactions between strains; Let’s think of a game of rock, paper, scissors with dozens of options. And the arms race has a history. Using ancient samples, the researchers show that many of the variations in these genes have existed for at least 200 years.

Evolutionary competitions are often seen as a simple one-on-one fight, probably because that’s an easy way to think about them. But the reality is that most are more like a chaotic bar fight, a fight in which it’s rare for one faction to gain a permanent advantage.

Science, 2024. DOI: 10.1126/science.ado0713 (About DOIs).

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