Some E. coli set off viral grenades inside nearby bacteria

Some bacteria can trigger unexploded viral grenades in neighboring bacteria’s DNA.

Certain Escherichia coli bacteria, including some that live in human intestines, make a chemical called colibactin. That chemical awakens dormant viruses inside nearby bacteria, sometimes leading to their destruction, researchers report February 23 in Nature.

This type of biological warfare among bacteria hasn’t been described before. “It’s an interesting strategy, and it’s also a dangerous strategy,” says Heather Hendrickson, an evolutionary microbiologist at the University of Canterbury in Christchurch, New Zealand, who was not involved in the work.

Colibactin producers must creep up on their bacterial enemies and trigger the unexploded ordinance hiding in the enemies’ DNA. Those grenades are prophages — bacteria-infecting viruses that have inserted themselves into their hosts’ DNA, where they hide out harmless and dormant until something triggers their awakening. That something, in this case, is DNA damage caused by colibactin.

When colibactin dings DNA, a bacterial repair system called the SOS response kicks in, chemical biologist Emily Balskus and colleagues found. “What many phages have done is to tap into that response,” says Balskus, a Howard Hughes Medical Institute investigator at Harvard University.

“It’s a signal for them to move out of this dormant lifestyle and awaken to kill their host and move on to find a new host,” she says. Once phages wake up, they replicate and burst out of the host cell, destroying it.

But once these viral grenades go off, they can infect other bacteria, potentially exposing the attacking bacteria and other close-by microbes to biological shrapnel.

Humans might also get caught in the cross fire. Researchers already knew that colibactin can cause damage to human DNA that may lead to colon cancer. But why the bacteria would use the chemical against people wasn’t known.

The new research suggests that E. coli may not be producing colibactin to assault its human hosts, but as a countermeasure against other microbes, Hendrickson says (SN: 12/14/21). “It’s easy to forget that there’s this continual conversation and warfare going on between bacteria, and we might not be the focus of their activities.”

Among bacteria, colibactin isn’t usually a lethal weapon. In most bacteria that Balskus and her colleagues examined, colibactin caused DNA damage, but the bacteria were able to repair the wounds. That may be because colibactin is an unstable chemical that quickly degrades before it can break enough DNA to do irreparable harm, Balskus says. Some bacteria also make other chemicals that defuse colibactin before it can damage DNA, her team found. Only bacteria that have unexploded prophages in their DNA and no other defenses were vulnerable to colibactin-producing bacteria in laboratory dishes.

Because colibactin decays quickly, “it suggests this is a very short-range communication,” says Michael Dougherty, a microbiome researcher at the University of Florida in Gainesville who was not involved in the study. “Maybe it could have an effect when bacteria are forming biofilms where you have trillions of bacteria stacked on top of each other.”

Colibactin may not be the only factor involved in exploding neighboring bacteria, says Dougherty’s University of Florida colleague Christian Jobin. Balskus’ team did not demonstrate that colibactin alone could detonate prophages. Perhaps something else about the colibactin-producing bacterium’s presence is required to kick off the fireworks, he suggests.

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 speculates.

“Maybe [colibactin] didn’t really evolve to kill. Maybe its primary ecological function involves doing something else,” she says. What that might be is a mystery that Balskus and her colleagues are working to solve.