Certain E. coli strains can engage in a form of bacterial warfare by producing colibactin, a chemical that can awaken long-dormant viruses inside neighboring cells’ DNA, sometimes resulting in their destruction, according to a new study published February 23 in Nature.
“It’s an interesting strategy, and it’s also a dangerous strategy,” Heather Hendrickson, an evolutionary microbiologist at the University of Canterbury in Christchurch, New Zealand, who was not involved in the work, tells Science News.
Throughout a bacterium’s life, bacteriophages—viruses that infect bacteria—insert their DNA into its genome. Typically, these embedded viruses, known as prophages, are harmless and lie dormant unless something triggers their escape. The study reports that E. coli can release colibactin, which damages neighbors’ DNA, triggering the bacteria’s DNA repair system, known as an SOS response. This releases prophage DNA from the bacteria’s genome, causing the virus to regain its virulence. Once these viruses are released from the bacterial genomes, they replicate and burst out of the host microbe, destroying it. They can also begin to infect other, neighboring bacteria—including the bacteria that released the colibactin.
Colibactin can damage DNA in mammalian cells. In humans, studies suggest that this damage can lead to colon cancer. The new study suggests that the colibactin may be a weapon bacteria use against other bacteria—not human hosts.
Colibactin isn’t usually lethal to bacteria. Although it caused DNA damage in most bacteria, the study’s authors report that the majority were able to repair the damage. According to Science News, this may be because colibactin is unstable and quickly degrades before it can do irreparable harm. The researchers also found that some bacteria make chemicals that can inhibit colibactin.
Colibactin’s quick decay “suggests this is a very short-range communication,” Michael Dougherty, a microbiome researcher at the University of Florida in Gainesville who was not involved in the study, tells Science News. “Maybe it could have an effect when bacteria are forming biofilms where you have trillions of bacteria stacked on top of each other.
Because colibactin is so ephemeral, it’s hard to study. That’s why Emily Balskus, a microbiologist at Howard Hughes Medical Institute, and her team used an indirect approach to study the compound, first examining its structure and determining that it likely forms bonds with, and then breaks, DNA’s double helix. Then, as the researchers were studying bacteria infected with prophages, they discovered that coculturing colibactin-producing bacteria with virus-infected bacteria caused a viral spike. They saw the same phenomenon with bacteria infected with multiple types of latent viruses. They also saw that coculturing colibactin-producing bacteria with virus-infected bacteria led to a decrease in the numbers of virus-containing bacteria.
Colibactin may not be acting alone. The team found that the chemical by itself could not reactivate prophages. The researchers were only able to see this effect by combining all of the chemicals the colibactin-producing bacteria produced and delivering them to other bacteria.
The researchers don’t yet know whether colibactin can trigger prophages when bacteria are in their natural habitats, such as human and other animal intestines. And perhaps awakening the viruses is an accident, Balskus tells Science News. She says she and her colleagues are continuing to work toward finding out whether that’s the case.