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The "Rapunzel" Virus: Evolutionary News

What is A Bacteriophage?

A bacteriophage, also known as a phage, is a type of virus that selectively targets, infects,

replicates in, and kills bacteria. They are acknowledged as the most abundant biological agent on earth and are widely distributed throughout the environment. There are thousands of varieties of phages, and each one can infect just one or a few unique types of bacteria. All bacteriophages are comprised of a nucleic acid molecule that is encased in a shield of phage-encoded capsid proteins, which fortify the genetic material and facilitate its passage into the next host cell. Bacteriophages can have head-and-tail, filamentous, or icosahedral (20-sided) capsids. Most phage have an additional tail (made of protein) that permits them to precisely identify a receptor on the surface of the host bacterium.

illustration of the Bacteriophage Virus that infects Stylized visualization of a bacteriophage. 3D illustration. Bacteriophage viruses infecting bacterial cells ,

and replicates within a bacterium. 3D illustration. Image Credit: Tatiana Shepeleva / Shutterstock Bacterial viruses. Image Credit: nobeastsofierce /

Image Credit: Tatiana Shepeleva / Shutterstock Shutterstock

The Rapunzel Virus

"A recent study in the Journal of Biological Chemistry has revealed the secret behind an evolutionary marvel: a bacteriophage with an extremely long tail. This extraordinary tail is part of a bacteriophage that lives in inhospitable hot springs and preys on some of the toughest bacteria on the planet."

One predator evolved "a monster of a tail" as a result of the endless arms race between viruses and bacteria over the course of billions of years. Although it is more popularly referred to as the "Rapunzel virus," the distinct bacteria-devouring virus, or bacteriophage, is officially identified by the designation P74-26. Phage tails, like hairstyles, vary in length and style; some are long and bouncy while others are short and stiff.

The "Rapunzel bacteriophage" has a tail that is 10 times longer than the majority of phages and is nearly 1 micrometer long, or around the breadth of some spider's silk. Most phages have modest, microscopic tails. The name "Rapunzel" comes from the classic fairy tale about a young woman with long blonde locks who was imprisoned in a tower by a wicked witch. The pathogen's "ponytail" stands out among its peers, much like the lost fabled princess with the unbelievably luscious locks. It actually has the longest tail of any virus that is currently known, and strangely enough, it also has the most stable tail.

P74-26 tail compared to most other phage tails. (Agnello et al., Journal of Biological Chemistry, 2023)

According to new research, this marvelous appendage is perhaps what enables the Rapunzel virus to pinpoint and puncture one of the toughest bacteria on Earth and in one of the most brutal environments. In order to penetrate bacteria, which are coated in a dense, viscous substance, phage tails are critical. The Rapunzel virus survives by infecting the bacteria Thermus thermophilus and using the other cell's machinery to replicate and multiply in bubbling hot springs that reach temperatures well over 77 °C (170 °F).

"Each phage tail is made up of many small building blocks that come together to form a long tube,” said Emily Agnello, a graduate student at the University of Massachusetts Chan Medical School and the lead author on the study."

“Our research finds that these building blocks can change shape, or conformation, as they come together. This shape-changing behavior is important in allowing the building blocks to fit together and form the correct structure of the tail tube.” Agnello said.

Bacteriophage P74-26 structure illustration. Credit: Leonora Martinez-Nunez

The components of the tail depend on one another to stabilize themselves, according to research using high-power imaging techniques and computer simulations.

“We used a technique called cryo-electron microscopy, which is a huge microscope that allows us to take thousands of images and short movies at a very high magnification,” Agnello said.

"By taking lots of pictures of the phage's tail tubes and stacking them together, we were able to figure out exactly how the building blocks fit together."

Bacteriophages have a vast scope of tail lengths and morphologies, including long, elastic, short, and stiff. Before entering and delivering their genome to the cytoplasm for replication, these molecular "machines" have evolved to recognize particular bacterial host cells.

They discovered that P74-26 renders itself robust using a "ball and socket" mechanism. Moreover, rings of molecules are stacked vertically to create a hollow canal in the tail.

“I like to think about these phage building blocks as kind of like Legos,” said Brian Kelch, an associate professor of biochemistry and molecular biotechnology at UMass Chan who supervised the work. “The Lego has studs on one side and the holes or sockets on the other.”

He added: “Imagine a Lego where the sockets start off closed. But as you start to build with the Legos, the sockets begin to open up to allow the studs on other Legos to build a larger assembly. This movement is an important way that these phage building blocks self-regulate their assembly.”

Bacteriophage with DNA RNA in fluid 3D illustration. Image Credit: Lucas Rayel / Shutterstock

According to Kelch, P74-26 requires half as many building blocks to create the stacking rings that make up the tail as most other phages do. As very few phage-host interactions have been studied to date and antibiotic resistance is becoming a greater concern to human health, experts are looking to phages for guidance on how to conquer superbugs.

“We think what has happened is that some ancient virus fused its building blocks into one protein. Imagine two small Lego bricks are fused into one large brick with no seams. This long tail is built with larger, sturdier building blocks,” Kelch explained. “We think that could be stabilizing the tail at high temperatures.”

Now, the scientists want to employ genetic engineering to tweak the phage's tail length and observe how it influences its behavior.

Microbiology concept. Bacteriophages on a blurred background. 3d illustration. Image Credit: vipman / Shutterstock

3d illustration Bacteriophage infecting bacterium. Image Credit: Design_Cells / Shutterstock


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