Long before humans became interested in killing bacteria, viruses were working to get rid of them. Bacteria-attacking viruses are called “phages” (short for bacteriophage), and were first identified by their ability to create bare patches on the surfaces of culture dishes covered with bacterial colonies. After playing a key role in the early development of molecular biology, many phages were developed as potential treatments that could be used when antibiotic resistance limits the effectiveness of conventional medicines.
But we’re relative latecomers when it comes to turning phages into tools. Researchers have described several examples where bacteria can retain pieces of disabled viruses in their genome and turn them into weapons that they can use to kill other bacteria that might compete for resources. I only learned about that weaponization recently, thanks to new research showing that this process has helped maintain diverse bacterial populations for centuries.
Killer Evolution
The new study began when the researchers were studying bacterial populations associated with feral plants in Germany, which included diverse members of the genus. PseudomonasThis includes plant pathogens. Usually, when bacteria infect a new victim, a single strain takes advantage of the host and grows dramatically. But in this case, Pseudomonas The population contained a variety of lineages that appeared to maintain stable competition.
To take a closer look, the researchers obtained more than 1,500 genomes from bacterial populations. More than 99 percent of these genomes contained viral fragments, with the average bacterial strain harboring chunks of two separate viruses in its genome. All of these were missing parts compared to functional viruses, suggesting they are the product of previously inserted viruses that were subsequently damaged and no longer function.
In and of itself, this isn’t surprising: many genomes (including our own) contain many disabled viruses. But bacteria tend to purge their genomes of unrelated DNA fairly quickly. In this case, a particular viral sequence appears to date back to a common ancestor of many strains, because the virus inserted itself in the same place in the genomes of all strains, and all instances of this particular virus were disabled by losing the same set of genes. The researchers named this sequence VC2.
Many phages have a typical structure: a large “head” containing the genetic material attached to the end of a stalk, which has “legs” at the end that help it cling to a bacterial victim. When the legs come into contact with a bacterial cell, the stalk contracts, helping to transfer the viral genome into the bacterial cell. In the case of VC2, all of its copies were missing the genes to make the head and all the genes needed to process the genome during infection.
This led the researchers to deduce that VC2 might be what they call a “tylosin” – a former phage that has been tamed by a bacterium and can be used to harm potential bacterial competitors. Bacteria with tylosins can produce partial phages consisting of only a leg and stalk. These tylosins can find and attach to other bacteria, but when the stalk shrinks, they have no genome to inject. Instead, they produce holes in the victim’s membrane, partially eliminating the cell’s borders and allowing some of its contents to leak out, leading to death.
Free evolutionary competition
To confirm that the VC2 sequence encoded tylosin, the researchers cultured bacteria containing the sequence, purified the protein from it, and used electron microscopy to confirm that they contained headless phages. When they exposed other bacteria to tylosin, they found that strains that produced tylosin were immune, but that many other strains growing in the same environment were killed by tylosin. When the team deleted the gene that coded for the main part of tylosin, the killing effect was abolished.
The researchers hypothesize that although this system is used to eliminate potential competitors, many strains of bacteria are developing resistance to tylosin.
When the researchers ran genetic screens to identify resistant mutants, they found that resistance was conferred by mutations that prevented the production of complex sugar molecules in proteins that attach to the outside of cells. At the same time, most of the genetic differences between the VC2 genes occurred in the proteins that code for the legs that attach to these sugars.
So every bacterial strain seems to be both aggressor and victim, and an evolutionary arms race is creating a complex set of one-to-one interactions between strains—think of a game of rock-paper-scissors with dozens of options. And this arms race has a history: Using old samples, the researchers show that many of these genetic mutations have been around for at least 200 years.
Evolutionary races are often seen as simple one-on-one battles, perhaps because it’s easy to think of them that way, but in reality most of them resemble chaotic barroom brawls in which no faction rarely gains a lasting advantage.
Science, 2024. DOI: 10.1126/Science.ado0713 (About DOIs)
