New phage could fight anthrax

Researchers at the University of Texas Medical Branch at Galveston have used an electron microscope and cryo-electron tomography to produce a three-dimensional image of a virus that infects anthrax bacteria.
Learning more about the bacteriophage, known as Bacillus anthracis spore-binding phage 8a, may provide scientists with an initial blueprint for using the phage in the detection and destruction of anthrax and other potential agents of bioterror.
"The images we made from these four major populations clearly show in three dimensions exactly how these remarkable nanodevices are able to penetrate the anthrax cell, release their DNA from the bacteriophage's head and ultimately control its flow through the phage tail and into the cell," Marc Morais, the senior author of the paper and an assistant professor at the University of Texas Medical Branch, said.
The phage's baseplate starts the process by binding to a suitable receptor on an anthrax bacteria. The binding causes the baseplate to alter its shape to an open, clawlike structure, signaling the phage's sheath to contract its length.
"When it contracts the tube has no choice but to be driven into the cell, much like a syringe," Morais said. "And in addition to contracting, the tail sheath is rotating, and that rotation exerts a torque on the neck protein, which opens the neck protein up so that DNA can now flow from the head into the tail, and then through the tail into the host cell's cytoplasm."
Morais and his colleagues would like to take advantage of the way SBP8a bonds to anthrax spores by employing them as a detection system for the deadly agent.
"We want to push to high enough resolution where we can see secondary structure and make reliable models, and really rationally engineer these type of things," Morais said. "The genome has been sequenced now, and we're figuring out which parts can be removed and replaced with green fluorescent protein — the first step to endowing these bacteriophages with a reporter capacity and making them a detection tool."
Morais said that by using different phages associated with different pathogenic bacteria, researchers may be able to identify many pathogens that could be involved in bioterror attacks.
"The great thing about our approach is that it is completely flexible. Every pathogenic bacterium has a phage associated with it," Morais said. "Thus, one could imagine tagging each pathogen-specific phage with a different colored signaling molecule such that you could make a cocktail of modified phages that glows a different color depending on which bacteria is present. Such a kit could be used to quickly identify a pathogen present in a bioterror attack."