Bacteria pass down their memories to fight viruses

In the invisible war between life forms, bacteria constantly fight off threats from viruses. These viruses, known as bacteriophages or simply “phages,” infect bacterial cells the same way human viruses attack our own bodies, leaving behind a memory of the invasion.

But unlike humans, bacteria don’t have white blood cells or antibodies. Instead, they use a genetic system called CRISPR to defend themselves. This ancient defense system is now drawing fresh attention from scientists.

Recent research from Johns Hopkins Medicine shows that bacteria don’t just defend passively. They actively gather pieces of viral code to remember their enemies. They pass these memories to their descendants.

Understanding this bacterial memory process may help us design new treatments for antibiotic-resistant infections – a growing global concern.

What are phages?

Phages get their name from the Greek word meaning “bacteria-eaters.”

These viruses either destroy their bacterial hosts or hide quietly inside them. That quiet phase is called dormancy. While dormant, the virus does not kill the host. Instead, it lives silently within the bacterial DNA.

Researchers have long wondered how bacteria survive the first wave of viral infection, especially from these temperate phages. The answer may lie in how bacteria collect and store genetic fragments from dormant viruses.

This behavior is not just survival; it’s preparation for the future.

Biological memory of viruses

In the Johns Hopkins study, researchers focused on Streptococcus pyogenes, the bacteria responsible for strep throat. They found that these bacteria take advantage of temperate phages during their inactive phase.

The bacteria gather genetic information from the phage while it’s dormant. This material forms a biological “memory” of the invader.

As the bacteria multiply, they pass this memory on. That means future generations are born with a built-in recognition system. When the same phage attacks again, the bacterial descendants already know how to defend themselves.

“We essentially wanted to answer the question: If bacterial cells don’t have any memory, or survival skills, to combat a new temperate phage that shows up, how do they buy themselves enough time to establish a new memory, before they succumb to that initial infection?” said Modell.

Bacteria use CRISPR to store viral memory

Bacteria use the CRISPR-Cas system to deal with phages. This system stores DNA from previous infections. When a known phage tries to re-enter, CRISPR recognizes its genetic material and destroys it.

Johns Hopkins researchers infected bacterial cells with both natural phages that go dormant and genetically modified phages that stay active. They wanted to see how the CRISPR system responded under both conditions.

“Our results indicate that the bacteria’s CRISPR system was more effective at using the naturally dormant phage to pull parts of the viral genetic code into their genome,” said Modell. “When we tested phages that could not go dormant, the CRISPR system did not work nearly as well.”

Dormant viruses boost bacteria memory

When phages go dormant, bacteria have more time. They use this period to build memory and prepare defenses. Researchers then allowed the surviving bacteria to multiply. They sequenced the DNA of these new generations.

The results were striking. The bacteria had collected hundreds of thousands of genetic “memories.” Each entry in the CRISPR system reflected past encounters with the virus. This memory-building happened mostly during dormancy, when the virus posed no immediate threat.

“This is conceptually similar to a vaccine with an attenuated virus,” said Nicholas Keith, a graduate student and first author of the paper.

“We believe this is the reason why the CRISPR Cas9 system has a unique relationship with this specific class of temperate phage.”

Understanding how the system works

Vaccines train human immune systems by introducing harmless versions of dangerous viruses. The CRISPR system appears to do something similar. Dormant phages act like training tools, helping bacteria prepare without putting their survival at risk.

“We can use these types of experiments to find what elements of the phage, the bacterial host and its CRISPR system are important for all stages of bacterial immunity,” explained Keith.

Researchers are especially interested in why the system works better with dormant viruses than with active ones. This information could shape how scientists use phages to treat bacterial infections in humans.

Future treatments and fighting resistance

Antibiotic resistance is a growing problem. Some bacterial infections no longer respond to any known drugs. Phage therapy – using viruses to attack bacteria – is one potential solution. But this approach only works if we understand how bacteria defend themselves.

“We know CRISPR systems are one of the first lines of defense against the transfer of hazardous genes from phages that turn bacterial cells toxic. Furthermore, our studies will inform the design of ‘phage therapies’ which could be used in clinical cases where a bacterial infection is resistant to all available antibiotics,” noted Modell.

Understanding CRISPR could help scientists fine-tune phage therapies. They could choose or design viruses that bacteria are less able to resist, leading to more effective treatments.

A collaborative effort

​The research was supported by multiple institutions, including the Johns Hopkins University School of Medicine, the National Institutes of Health, the Rita Allen Foundation, and the National Science Foundation.​

In addition to Nicholas Keith and Joshua Modell, the team included Rhett Snyder from Johns Hopkins and Chad Euler from Hunter College. Their combined efforts push us closer to smarter, safer ways of managing infections that resist current drugs.

In the end, studying bacteria doesn’t just teach us about microbes. It shows us new paths to protect ourselves, using lessons written in the smallest pieces of life.

The study is published in the journal Cell Host & Microbe.

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