How Zombie Viruses are Awakened by some Gut Microbes
Gut bacteria produce a wide range of chemicals, but we don’t know what the majority of them do. A new study suggests that one of these compounds, previously linked to cancer, could be used as a bizarre weapon in microbial battles.
Microbiome and Role of Gut Bacteria
The human body has approximately 30 trillion cells. But it’s also home to around 39 trillion bacteria. Together with fungi and viruses, they form a vast community called the microbiome.
The largest and most diverse population of bacteria is found in the gut, with thousands of different types inside our intestines. These microbes may be tiny, but they play a huge role in our health. They help train the immune system, so it knows what to eliminate or ignore. They also help us digest food.
Role of Gut Bacteria in Cancer
Scientists now think gut bacteria play a role in how some cancers start and maybe even how these cancers respond to treatment. Inflammation happens when the cells in our bodies become damaged or infected. And molecules released during long periods of gut inflammation can push normal cells towards becoming cancerous. Certain types of gut bacteria may be behind the bout of inflammation responsible for starting some bowel cancers.
Deadly Virus can be Awakened by Gut Microbes
Certain gut bacteria have a strange superpower: they can resurrect viruses that have been dormant in other microbes.
This viral awakening causes full-fledged infections that destroy virus-carrying cells, according to research from Howard Hughes Medical Institute Investigator Emily Balskus’ lab, which was first published as a preprint on a website and then in the journal called Nature. They discovered that the deadly viruses can be awakened by a mysterious chemical called colibactin.
Colibactin | Bacterial Toxin or Mediator of viruses
Microbes frequently produce noxious compounds to attack one another within the gut’s cramped quarters. However, according to Balskus, a chemical biologist at Harvard University, colibactin appears to be unique among these chemical weapons. “It doesn’t directly kill the target organisms, which is what we normally think of bacterial toxins doing within microbial communities.” Instead, colibactin modifies microbial cells in such a way that it activates latent – and lethal – viruses hidden in the genomes of some bacteria.
Microbes have long been sought after for their powerful chemicals.”We know a lot about their chemical properties, purify them in the lab and use them as medicine, including antibiotics,” says Breck Duerkop, a professor of medicine at the University of Colorado. However, why bacteria produce these compounds and what effects they have on neighboring organisms are unanswered questions, according to Duerkop, who was not involved in this study. He describes Balskus’s new work as a “step in the right direction.”
Colibactin | Havoc to human cells
For years, scientists have known that colibactin can cause havoc on human cells. According to Balskus and others’ research, the compound damages DNA, which can lead to colorectal cancer. However, establishing a link between this compound and disease proved particularly difficult.
A French team reported in 2006 that mammalian cells exposed to the gut bacteria E. coli suffered fatal DNA damage. This damage was linked to a cluster of E. coli genes that encode machinery for the construction of a complex molecule, according to the researchers. The molecule, dubbed colibactin, was extremely difficult to study. Despite several attempts, researchers were unable to extract it from the E. coli that was creating it.
Chemical Dark Matter Colibactin
Colibactin is one of several ephemeral compounds that scientists suspect microbes produce. This “chemical dark matter,” like invisible particles of dark matter in space, necessitates novel methods of investigation. Balskus investigates these elusive molecules indirectly as part of her research into the microbial chemistry of the gut.
Her team has investigated colibactin over the last ten years by studying the microbial machinery that produces it. She and her colleagues pieced together the structure of colibactin and discovered that it damages DNA by forming errant connections within the double helix.
Based on this research, other researchers discovered a definitive link to cancer: the molecule’s unique fingerprints appear in genes known to drive colorectal tumor growth.
The most recent colibactin trial conducted by Balskus started with a different disease: COVID-19. Her lab, like many others, had to rearrange things to reduce physical contact among researchers. Postdoc Justin Silpe and graduate student Joel Wong ended up working next to each other for the first time as a result of the reshuffling. Their discussions led them and Balskus to speculate on how colibactin affected other microbes in a crowded gut.
They discovered early on that exposing colibactin-producing bacteria to non-producers had little effect, implying that the molecule isn’t particularly lethal on its own. Silpe and Wong were unsure whether colibactin, a large, unstable molecule, could even enter bacterial cells and cause DNA damage. They then wondered if there was a third party involved, such as bacteria-infecting viruses. These viruses, which are little more than bits of genetic information, can slip into bacteria’s DNA and lurk in the shadows. Then, when activated, they cause an infection that explodes the cell like a landmine.
When the researchers grew colibactin producers alongside bacteria containing such latent viruses, they observed an increase in viral particles spike and a decrease in the growth of many virus-containing bacteria. This suggested that the molecule caused an increase in active, cell-killing infections. The team demonstrated that colibactin enters bacteria and damages DNA. This damage sets off a cellular alarm, rousing the viruses.
Many microbes appeared to be able to defend themselves against colibactin. Balskus’ team discovered a resistance gene that encodes a protein that neutralizes the compound in a wide range of bacteria.
Though colibactin is dangerous, it may serve as more than just a lethal weapon, according to Balskus. For example, both DNA damage and awakened viruses can cause genetic changes in neighboring bacteria rather than death, potentially benefiting colibactin producers.
The findings of Balskus’ team suggest that cancer may be collateral damage to whatever else colibactin-producing bacteria are doing. She continues, “We’ve known for a long time that bacteria created this poison to kill other bacteria.” “It didn’t make sense from an evolutionary standpoint to get it to target human cells.”
Balskus intends to investigate how the compound affects the microbiome community in the gut, specifically which microbes disappear and which thrive after exposure to the compound. “Understanding the influence of colibactin on the microbes and how it is managed could be the answer to cancer prevention,” she says.
Very informative content