Ancient viruses inside bacteria may help fight infections

For billions of years, bacteria and viruses have engaged in constant battles. We generally think of bacteria as bad, but viruses as worse.

The truth is more nuanced: some bacteria have ancient viruses inside them – and these bits of old viruses may actually help bacteria fend off new viral invaders.

Now, scientists are looking at how this strange defense system works, and how it might be useful in medicine and food production.

Ancient viruses as bacterial bodyguards

Some bacteria carry bits of viral DNA tucked inside their own genetic code. These aren’t active viruses – they’re ancient ones, called cryptic prophages, that stopped being harmful a long time ago.

But the viruses stuck around. And in some cases, they actually help the bacteria survive attacks from new viruses.

A research team set out to understand how that works. They looked at bacteria with these quiet viruses and found something unexpected.

When a new virus shows up, an enzyme called recombinase – specifically one named PinQ – jumps into action. It flips a section of the bacterial DNA, which ends up creating two new proteins called Stf proteins.

Those proteins act like a shield, keeping the virus from locking onto the bacteria and injecting its own DNA. It’s a kind of internal defense system that works only when triggered by a threat.

Bacteria fine-tune their virus defense

“It’s remarkable that this process actually produces new chimeric proteins, specifically from the inverted DNA – most of the time when you change DNA, you just get genetic mutations leading to inactive proteins,” said Thomas Wood, who led the study.

“These inversions and adaptations are clear evidence that this is a fine-tuned antivirus system that has evolved over millions of years.”

Wood, a professor of chemical engineering at Penn State, explained that until now, scientists had noticed recombinase enzymes near virus-related genes in bacteria, but didn’t understand what they were doing.

“It’s not that researchers missed these enzymes, it’s that they saw them and overlooked them as mere markers of virus genes,” he said.

What the team discovered is that recombinase isn’t just sitting around. It’s actively helping bacteria defend themselves when viruses show up.

Rethinking how we treat infections

Here’s why this matters: Antibiotic resistance is becoming a huge problem. Many bacteria have evolved to survive the drugs we use to kill them. As a result, doctors are running out of treatment options.

One possible solution? Use viruses called phages to target and destroy harmful bacteria.

“Antibiotics are failing, and the most likely substitute is viruses themselves. Before using viruses as antibiotic replacements to treat human infections, however, we must understand how the bacterium defends itself from viral attack,” said Wood.

By studying how bacteria fight back with help from cryptic prophages, researchers can figure out which bacteria are vulnerable to phages – and which ones might put up a fight.

When viruses push back

To test the defense system, the team added extra Stf proteins to E. coli bacteria and then introduced viruses.

After letting the mixture sit overnight, they checked how cloudy it was. If the mixture stayed cloudy, that meant the viruses had been stopped and couldn’t infect the bacteria.

The researchers also used computer simulations to double-check how the viruses tried to attach to the bacteria.

“When we overproduce the protein, we initially stop the virus from landing on the cell surface,” Wood said. “After eight experimental iterations, however, the virus changes its landing proteins – how it identifies and attaches to the bacteria – and can get by this defense.”

That’s part of the challenge. Viruses evolve quickly. But even short-term protection could be helpful, especially in food production and medical settings.

More ancient viral defenses to uncover

“This is a story about how a fossil protects its host from the outsider, and we have 10 other fossil-related stories that could offer their own defenses waiting to be tested,” said Wood.

The team plans to explore other cryptic prophages to see if they offer similar antivirus benefits.

A deeper understanding of these systems could help scientists safely use bacteria in everything from food fermentation to bioengineering and infection control.

By looking to the past – inside the DNA of ancient viruses – researchers are finding clues that could help shape the future of medicine.

The full study was published in the journal Nucleic Acids Research.

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