A recent study in Journal of Biological Chemistry revealed the secret behind an evolutionary miracle: a bacteriophage with an extremely long tail. This amazing tail is part of a bacteriophage that lives in inhospitable hot springs and hunts down some of the toughest bacteria on the planet.
Bacteriophages are a group of viruses that infect and reproduce in bacteria and are the most common and diverse things on Earth.
“Bacteriophages, or phages for short, are found everywhere in bacteria, including in the dirt and water around you, as well as in your body’s microbial ecosystem,” said Emily Agnello, a graduate student at the University of Massachusetts Chan Medical School and lead author. author in the study.
Unlike many of the viruses that infect humans and animals that contain only one compartment, phages consist of a tail attached to a sharp, prism-like protein shell that contains their DNA.
Pigtails, like hairstyles, vary in length and style. Some are long and puffy while others are short and stiff. While most phages have short, tiny tails, the “Rapunzel bacteriophage” P74-26 has a tail 10 times longer than most and is almost 1 micrometer long, about the width of some spider silk. The nickname “Rapunzel” comes from the fairy tale in which a girl with extremely long hair was locked in a tower by an evil witch.
Brian Kelch, an associate professor of biochemistry and molecular biotechnology at UMass Chan, who supervised the work, described P74-26 as a “monster of a tail.”
Phage tails are important for piercing bacteria, which are coated in a thick, viscous substance. The long tail of P74-26 allows it to invade and infect the toughest bacteria. Not only does P74-26 have an extremely long tail, but it is also the most stable phage, allowing it to exist and infect bacteria that live in hot springs that can reach over 170° F. Researchers have studied P74- 26 learn why and how it can exist in such extreme environments.
To work with a phage that thrives at such high temperatures, Agnello had to adjust the conditions of her experiments to get the phage’s tail to assemble in a test tube. Kelch said Agnello created a system by which she could induce rapid self-assembly of the tail.
“Each phage tail is made up of many small building blocks that come together to form a long tube. Our research finds that these building blocks can change shape or configuration as they come together,” Agnello said. “This shape-changing behavior is important to allow the building blocks to fit together and form the correct structure of the tail pipe.”
The researchers used high-powered imaging techniques as well as computer simulations and found that the structural elements of the tail rested on each other to stabilize themselves.
“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 very high magnification,” Agnello explained. “By taking many pictures of phage tail tubes and stacking them together, we were able to understand exactly how the building blocks fit together.”
They found that the P74-26 uses a “ball and socket” mechanism to hold up. In addition, the tail is formed by vertically stacked rings of molecules that create a hollow channel.
“I like to think of these phage building blocks as Legos,” Kelch said. “Lego has studs on one side and holes or slots on the other.”
He added: “Imagine a Lego where the sockets start out closed. But as you start building with the Legos, the sockets start to open up to allow studs into other Legos to create a larger assembly. This movement is an important way to these phage building blocks self-regulate their assembly.”
Kelch pointed out that, compared to most phages, P74-26 uses half the number of building blocks to form the stacked rings that make up the tail.
“We think what happened is that some ancient virus joined its building blocks into a protein. Imagine two small Lego bricks merging into one big brick without seams. This long tail is built with larger, sturdier building blocks,” he explained. Kelch. “We think this could stabilize the tail at high temperatures.”
The researchers now plan to use genetic manipulation to change the length of the phage’s tail and see how this changes its behavior.
Phages occupy almost every corner of the planet and are important to a variety of industries such as healthcare, environmental conservation and food safety. In fact, long-tailed phages such as P74-26 have been used in preliminary clinical trials to treat certain bacterial infections.
“Bacteriophages are gaining ever-increasing interest as an alternative to antibiotics for the treatment of bacterial infections,” Agnello said. “By studying phage assembly, we can better understand how these viruses interact with bacteria, which could lead to the development of more effective phage-based therapies. … I think studying unique, interesting things can lead to discoveries and applications that we can” you can’t even imagine”.