【Nature】Superpower?

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Author: Ashley Introduction: A recent study found that a genotoxin, colibactin, has a superpower that can wake up dormant viruses in "neighbors"
.

A bacterial natural product of particular relevance to human health, colibactin, is a chemically unstable small-molecule genotoxin produced by several different bacteria, including members of the human gut microbiome
.

The research suggests that the key to preventing cancer may be understanding the effects of colibactin on the microbial community, and how to control its production
.

Some gut bacteria have a creepy superpower: they can "revive" dormant viruses that lurk inside other microbes
.

This viral awakening unleashes a full-blown infection that destroys virus-carrying cells, first published as a preprint on bioRxiv by the lab of Howard Hughes Medical Institute investigator Emily Balskus, and subsequently published on February 23, 2022 in Published in the journal Nature, titled "The bacterial toxin colibactin triggers prophage induction"
.

They found that a stealthy molecule called colibactin can wake up a dormant killer virus
.

Microbes often attack each other by producing toxic compounds in the narrow zone of the gut
.

But among these chemical weapons, colibactin appears unusual, says Harvard chemical biologist Balskus: "It doesn't kill the target organism directly, which is what we normally think of bacterial toxins do within microbial communities
.

" Instead , colibactin fine-tunes microbial cells to activate deadly viruses lurking in the genomes of certain bacteria
.

Humans have long searched for potent compounds produced by microorganisms
.

"We know a lot about their chemistry, we purify them in the lab, and we use them as medicines, including antibiotics," said Breck Duerkop, who studies bacterial viruses at the University of Colorado School of Medicine,
but
was not involved in the study.
Why bacteria make these compounds and what effect they have on neighboring organisms is an open question, Duerkop said
.

He called the new study by Balskus' team: "a step in the right direction
.

" "Chemical dark matter" Scientists have known for years that colibactin can wreak havoc on human cells
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Research by Balskus and many others has shown that the compound damages DNA, which can lead to colorectal cancer
.

But establishing a link between the compound and disease has proved particularly difficult
.

In 2006, a French research team reported that mammalian cells encountered E.
coli suffered fatal damage to their DNA
.

The researchers linked this damage to a cluster of E.
coli genes that code for building complex molecular mechanisms
.

The molecule, called colibactin, is very difficult to study
.

After many attempts, the researchers simply couldn't isolate it from the E.
coli that made it
.

Colibactin is one of many short-lived compounds that scientists suspect microbes produce
.

Like invisible particles of dark matter in space, this "chemical dark matter" requires creative means to study
.

As part of her exploration of gut microbial chemistry, Balskus uses indirect methods to detect these elusive molecules
.

For the past 10 years, her team has explored colibactin by studying the microbial mechanisms that make it
.

She and her colleagues pieced together the structure of colibactin and determined that it damages DNA by forming false connections within the double helix
.

Building on this work, scientists elsewhere have revealed a definitive link to cancer: The molecule's unique fingerprint appears in genes known to drive colorectal tumor growth
.

The role of viruses Balskus' recent colibactin study begins with another disease: COVID-19
.

Like many other labs, she had to rearrange to reduce physical contact between researchers
.

As part of the reorganization, postdoc Justin Silpe and graduate student Joel Wong are working together for the first time
.

Their conversation left them and Balskus wondering how colibactin affects other microbes in a crowded gut
.

Early on, they found that exposing colibactin-producing bacteria to non-producers had little effect, suggesting that, on its own, the molecule isn't particularly deadly
.

Silpe and Wong were unsure whether colibactin, an unstable macromolecule, could even enter bacterial cells and damage their DNA
.

Then, they wondered if a third party -- a virus that infects bacteria -- might be involved
.

With just some genetic information, these viruses can slip into the DNA of bacteria and wait in silence
.

Once triggered, they cause an infection that blows up cells like landmines
.

When the researchers incubated colibactin producers with bacteria that carried the latent virus, they saw a surge in the number of viral particles and a drop in the growth of many virus-containing bacteria
.

This suggests that the molecule triggers a surge of active, cell-killing infection
.

The team showed that colibactin does enter bacteria and damage DNA
.

This damage sounds like a cellular wake-up call for the virus
.

Many microbes appear to have the ability to protect themselves from colibactin
.

Balskus' lab identified a resistance gene that encodes a protein that neutralizes the compound in a variety of bacteria
.

While colibactin clearly has a dangerous side, it may be more than a lethal weapon, Balskus said
.

For example, DNA damage and awakened viruses can also induce genetic changes in neighboring bacteria, rather than death, potentially benefiting colibactin producers
.

The findings of Balskus' group suggest that cancer may be a collateral damage caused by any other colibactin-producing bacteria
.

"We've always suspected that bacteria make this toxin to target other bacteria in some way
.

From an evolutionary perspective, it doesn't make sense that they acquired it to target human cells, " she said
.

Next, Balskus plans to study how the compound alters the microbial community in the gut -- which microbes disappear after exposure to the compound and which thrive
.

"The key to cancer prevention may be understanding the effect of colibactin on the microbiome," she said.
, and how to control its production
.

"Reference: https://medicalxpress.
com/news/2022-02-gut-microbes-awaken-zombie-viruses.
html Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment plans
.

For health guidance , please go to a regular hospital for treatment.
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