Diagram of bacteriophages

Stages can sense bacterial DNA damage, which prompts them to replicate and jump ship.

Viruses may be ‘watching’ you – some microbes wait for their host to give them a signal to start replicating and kill them.

Especially after more than two years[{” attribute=””>COVID-19 pandemic, many people picture a virus as a nasty spiked ball – essentially a mindless killer that gets into a cell and hijacks its machinery to create a gazillion copies of itself before bursting out. For many viruses, including the coronavirus that causes COVID-19, the “mindless killer” moniker is essentially true.

However, there’s more to virus biology than meets the eye.

A suitable illustration is HIV, the virus that causes AIDS. HIV is a retrovirus that does not immediately go on a killing spree when it enters a cell. Instead, it integrates itself into your chromosomes and chills, waiting for the proper opportunity to command the cell to make copies of it and burst out to infect other immune cells and eventually cause AIDS.

Bacteriophages, or simply phages, are naturally occurring viruses that attack and kill bacteria. They cannot infect human cells. Phages are extremely diverse and exist everywhere in the environment, including in our bodies. In fact, humans contain more phages than human cells.

A phage has three main parts: a head, a sheath, and a tail. The phage uses its tail to attach to a bacterial cell. They use the bacteria to replicate themselves. After finding a “matching” bacterial cell, the phage injects its genetic material, hijacking the system normally used for bacterial reproduction. Instead the system will make thousands more phages, which ultimately burst the bacterial cell, releasing it into the environment.

Exactly what moment HIV is waiting for is not clear, as it’s still an area of active study. However, research on other viruses has long indicated that these pathogens can be quite “thoughtful” about killing. Of course, viruses cannot think the way you and I do. But, as it turns out, evolution has bestowed them with some pretty elaborate decision-making mechanisms. For example, some viruses will choose to leave the cell they have been residing in if they detect DNA damage. Not even viruses, it appears, like to stay on a sinking ship.

For over two decades, my laboratory has been studying the molecular biology of bacteriophages, or phages for short, the viruses that infect bacteria. Recently, my colleagues and I demonstrated that phages can listen for key cellular signals to help them in their decision-making. Even worse, they can use the cell’s own “ears” to do the listening for them.

Escaping DNA damage

If the enemy of your enemy is your friend, phages are certainly your friends. Phages control bacterial populations in nature, and clinicians are increasingly using them to treat bacterial infections that do not respond to antibiotics.

The best-studied phage, lambda, works a bit like HIV. Upon entering the bacterial cell, lambda decides whether to replicate and kill the cell outright, like most viruses do, or to integrate itself into the cell’s chromosome, as HIV does. If the latter, lambda harmlessly replicates with its host each time the bacteria divides.

This video shows Lambda Phage E. coli contamination.

However, a job like HIV Lambda is not just sitting around. It uses a special protein called CI as a stethoscope to listen for signs of DNA damage inside the bacterial cell. If the bacteria’s DNA is damaged, that’s bad news for the lambda phage housed inside. Damaged DNA leads directly to the evolutionary garbage can because it is useless to the phage needed for reproduction. So lambda turns on the replication genes, makes copies of itself, and wants to break out of the cell and infect other intact cells.

Tapping the cell communication system

Instead of gathering intel with their own proteins, some phages knock out the infected cell’s DNA damage sensor, LexA.

They are proteins such as CI and LexA. transcription factors It turns genes on and off by binding to specific genetic patterns in the DNA handbook that is the chromosome. They found that some phages, such as coliphage 186, do not need their own viral CI protein if they have short DNA sequences in their chromosomes that can contain bacterial LexA. When it detects DNA damage, LexA activates the phage’s replication-killing genes, essentially doubling over the cell to self-destruct and allowing the phage to escape.

Researchers first reported the role of CI in phage decision making In the 1980s and Coliphage 186’s counterintelligence strategy In the late 1990s. Since then, there have been a few other reports of bacteria hitting communication systems. It is one example. phage phi29The bacterium takes advantage of the host’s transcriptional status when preparing to produce a spore or a bacterial egg. Able to survive harsh environments. Phi29 instructs the cell to pump its DNA into the spore, killing the growing bacteria after the spore germinates.

Transcription factors turn genes on and off.

in A recently published studyMy colleagues and I show that several groups of phages have independently evolved the ability to enter the CtrA protein into another bacterial communication system. CtrA integrates multiple intrinsic and extrinsic signals to activate various developmental processes in bacteria. The most important of these is the production of bacterial substances Flagella and pili. As it turns out, these phages attach to the pili and flagella of bacteria to infect themselves.

Our leading hypothesis is that phages use CtrA to predict when there will be enough bacteria to readily infect nearby sport pili and flagella. Pretty clever trick for a “mindless killer”.

These aren’t the only ones making elaborate decisions – they all have brains, but they’re useless. Some phages that infect Bacillus Each time a bacterium infects a cell, it produces a small molecule. The phages can recognize and use this molecule. Count the number of phage infections It is happening around them. As with alien invaders, this count helps determine when to switch on their reproductive and lethal genes, killing only when hosts are relatively outnumbered. In this way, the phages ensure that they do not run out of hosts to infect and guarantee their own long-term survival.

Antiviral antipsychotics

A good question is why you should care about counterintelligence ops run by bacterial viruses. While bacteria are very different from humans, the viruses that infect them are. It is not different From viruses that attack people. so beautiful Every single method It was later shown that a person who plays with phages can be used by viruses. If a phage can touch bacterial communication lines, why can’t a human virus touch yours?

So far, scientists don’t know what human viruses might hear if they hijack these lines, but there are several possibilities to consider. Like phages, I believe that human viruses can be counted on to strategize, detect cell growth and tissue formation, and monitor immune responses. For now, these possibilities are just speculation, but scientific research is underway to investigate.

Listening to viruses of your cell’s private conversations isn’t the funnest of pictures, but it’s not without a silver lining. As intelligence agencies around the world know all too well, counterintelligence only works when it’s secret. Once detected, the system can be easily exploited to feed false information to an adversary. Similarly, I believe that future anti-viral treatments may combine conventional artillery, such as anti-virals that prevent virus replication, with information warfare manipulation, such as tricking the virus into believing that the host cell is a different tissue.

But keep quiet and don’t tell anyone. You may be listening to viruses!

Written by Evan Ariel, Associate Professor of Biological Sciences, University of Maryland, Baltimore County.

This article was first published in The conversation.The conversation

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