Researchers from the University of Alabama at Birmingham used cryo-electron microscopy to reveal the structure of a bacterial virus in unprecedented detail. This is the first known structure of a virus capable of infecting Staphylococcus epidermidis, and the high-resolution structural information is crucial to understanding viral biology and the possibility of using the virus as a treatment for bacterial diseases.
The term "phages" or "bacteriophages" refers to viruses that infect bacteria. At the University of Illinois Urbana-Champaign, Dr. Along with Asma Hatoum-Aslan, Dr. The UAB team, led by Terje Dokland, identified atomic patterns for all or part of 11 different structural proteins in the Andhra phage. Science Advances published this study.
It belongs to the Andhra picovirus family. The only host it accepts is S. epidermidis. Although largely harmless, this skin bacterium is a major contributor to persistent medical equipment infections. Hatoum-Aslan, a phage biologist at the University of Illinois, noted that "picoviruses have been detected infrequently in phage collections and have not been adequately researched and abused for therapeutic applications."
The emergence of antibiotic resistance in a similar pathogen, Staphylococcus aureus and S. epidermidis, has rekindled interest among researchers in the possibility of exploiting bacteriophages to treat bacterial infections. After attaching to the bacterial cell wall, breaking it enzymatically, puncturing the cell membrane and injecting viral DNA into the cell, picoviruses inevitably cause the death of the cells they infect.
In addition, other features such as having a small genome and inability to transfer bacterial genes between bacteria make them attractive candidates for therapeutic applications.
Once familiar with the Andhra protein structure and understanding how these structures allow the virus to infect a bacterium, it will be possible to create customized phages using genetic engineering.
Dokland, professor of microbiology at UAB, said, “S. The structural basis of host specificity between phages infecting S. aureus and S. epidermidis is still poorly known.”
“With the help of current research, we are opening the door to more sensible bespoke phage design for therapeutic purposes by gaining a better understanding of the structures and functions of Andhra gene products, as well as factors influencing host specificity. Our research reveals key features for virion assembly, host recognition and host penetration.”
Because the surface teichoic acid polymers of various bacterial species differ, staphylococcal phages normally infect only a small subset of bacteria.
It is possible because of their limited host range that phages can only target the particular disease-causing pathogen, but this also means that the phage may need to be individualized in each individual case.
Andhra is a 20-sided icosahedral capsid that is usually round in shape and houses the viral genome. A short tail has been added to the cap. The tail is mostly involved in attaching to S. epidermidis and catalyzing the breakdown of its cell wall. Via the tail, the bacterium receives the viral DNA. The trunk, appendages, mace, and tail end, as well as the passage from the capsid to the tail, are all considered tail segments.
Each virus particle consists of multiple copies of the 11 different proteins that make up it. For example, the copy number of the nine proteins that make up a virion ranges from two to 72, while the capsid consists of 235 copies of each of the two proteins.
The 12th protein whose structure was predicted using the protein structure prediction program AlphaFold is one of the 645 protein fragments that make up the virion.
The structure of each protein was determined by Dokland, Hatoum-Aslan, and first authors James L. Kizziah, Ph.D., N'Toia C. Hawkins, Ph.D. of the UAB Department of Microbiology. and N'Toia C. Hawkins, Ph.D. illustrated in the models of atoms developed by These structures are expressed in molecular terms such as alpha-helix, beta-helix, beta. The researchers described how each protein interacts with different types of neighboring proteins and how each protein binds to other copies of the same protein type to form the hexameric and pentameric faces of the capsid.
Electron microscopes, which have much higher resolution than light microscopes, illuminate an item using an accelerated beam of electrons. With the addition of supercold temperatures, cryo-electron microscopy is particularly useful for unraveling the atomic structure of larger proteins, membrane proteins, or complexes of various biomolecules as well as lipid-containing materials such as membrane-bound receptors.
New electron detectors have significantly increased the resolution of the cryo-electron microscope over the traditional electron microscope over the past eight years. The following are key components of what has been called the "resolution revolution" in cryo-electron microscopy:
Aqueous samples were flash-frozen in ethane cooled to below -256 degrees Fahrenheit. Instead of ice crystals that damage samples and scatter the electron beam, the water freezes into window-like "glassy ice".
To preserve the proteins, the sample is kept extremely cold under the microscope and only receives a small amount of electrons.
With the ability to count individual atoms at hundreds of frames per second, extremely fast direct electron detectors provide real-time correction of sample motion.
Thousands of photos are combined using advanced computation to create three-dimensional structures with perfect resolution. Terabytes of data are processed by graphics processing units.
To create a three-dimensional tomographic image similar to a CT scan in a hospital, the microscope stage holding the sample can be tilted as images are captured.
UAB researchers began studying Andhra virion structure with 230.714 particle images. With 186.542, 159.489, 159.489, 159.489, and 159.489 images, the capsid, tail, distal tail, and tail tip were the first to undergo molecular reconfiguration. Resolution was in the range of 3.50-4.90 angstroms.
Source: phys.org/news
Günceleme: 19/12/2022 20:41
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