Researchers from the Howard Hughes Medical Institute have shown in a new study how certain microbes cause out-of-action viruses in their neighbors to reactivate and destroy cells containing them.
These microbes do this by the means of a molecule known as colibactin. This compound is just one of numerous that bacteria make to attack their neighbors within a teeming gut. It does not kill other microbes directly, as bacterial toxins are often thought to do. Rather, it works to trigger latent viruses back to life and so leads to full-scale, lethal infections.
The study done at the lab of Emily Balskus was first released as a bioRxiv preprint. It was later published in Nature.
Threat of colibactin
Scientists have been studying the compounds that bacteria produce to assail one another. But it was not fully clear how these toxins impact nearby microbes.
It has been known for some years that colibactin poses a great threat to human cells. Scientists, including Balskus, have found that it causes damage to DNA and this can result in colorectal cancer.
However, it has proven quite difficult to establish a link between colibactin and disease. Researchers liken the compound to “chemical dark matter,” which requires extra ingenuity to probe.
Some French researchers had observed in a 2006 study that cells in mammals that were exposed to the bacteria E. coli felt fatal DNA damage. They tried without success to isolate colibactin after detecting it played a part in the damage.
Balskus and her team have been studying the molecule using indirect approaches. They have succeeded in assembling its structure and showing that it leads to DNA damage through the creation of abnormal connections.
Resurgence of dormant viruses
Researchers in this study first observed that exposing bacteria making colibactin to others that do not produce it made little difference. They assumed, as a result, that the molecule solely is not very deadly.
The team, therefore, speculated if other agents, such as viruses, played a part in attacks. These bugs can get into the DNA of bacteria and lie there dormant. Full-blown infections can result once these viruses are set off.
To put their theory to the test, researchers grew colibactin-producing bacteria alongside those having dormant viruses. This led to a surge in the number of viral particles and a decline in the growth of virus-carrying microbes.
The team confirmed that colibactin does get into bacteria and damage DNA. The compound promotes a dramatic rise in active infections that threaten cells by reanimating latent viruses.
Findings by Balskus and her team suggest that cancer may be due to damage caused by bacteria that make colibactin.
“We always suspected that bacteria made this toxin to target other bacteria in some way,” Balskus said. “It didn’t make sense from an evolutionary perspective that they acquired it to target human cells.”
The researchers observed that many microbes seemed to be able to shield themselves against colibactin. They discovered a resistance gene that encodes a protein for thwarting the molecule in other microbes.
Balskus is now planning to examine how colibactin changes the balance of gut microbes. She and her team will aim to identify the bacteria that thrive and those that decline as a result of exposure to the molecule.
“The key to preventing cancer may be understanding the effects colibactin has on the microbe community and its production is controlled,” Balskus said.
Other research has shown a strong link between colibactin and genes that play a part in colorectal tumor growth.