A toxin called colibactin awakens dormant
viruses embedded in bacterial DNA
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.
Questions or comments on this article? E-mail
us at feedback@sciencenews.org
CITATIONS
J.E. Silpe, et al. The bacterial toxin
colibactin triggers prophage induction. Nature. Published online February 23,
2022. doi: 10.1038/s41586-022-04444-3.
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