A University of Otago – Ōtākou Whakaihu Waka-led study has produced a detailed blueprint of a bacteriophage, furthering their potential in the fight against drug-resistant bacteria.
Lead author Dr James Hodgkinson-Bean, who completed his PhD in the Department of Microbiology and Immunology, says bacteriophages are "extremely exciting" in the scientific world as researchers search for antibiotic alternatives to combat the increasing risk of antimicrobial resistance.
"Bacteriophage viruses are non-harmful to all multi-cellular life and able to very selectively target and kill a target bacterium. Due to this, they are increasingly being researched and applied in 'phage therapy' to treat highly drug-resistant bacteria," he says.
He describes bacteriophages as "exquisitely intricate viruses" which infect bacteria through large mechanical structures described as 'tails'.
For the study, published in Science Advances, researchers from Otago and the Okinawa Institute of Science and Technology explored the structure of Bas63, a virus which targets E. coli, in molecular detail to understand how their tail works during infection.
"This kind of research is important for understanding how we can select the optimal bacteriophages for therapies, and to understand the differences in infectious behavior we see in the lab," Dr Hodgkinson-Bean says.
Senior author Associate Professor Mihnea Bostina, also of Otago's Department of Microbiology and Immunology, says, with antibiotic resistance rising and plant pathogens threatening global food security, bacteriophages offer a promising alternative.
"Our detailed blueprint of a bacteriophage advances rational design for medical, agricultural, and industrial applications, from treating infections to combating biofilms in food processing and water systems.
"Beyond science, the 3D data – which shows the virus' rare whisker-collar connections, hexamer decoration proteins, and diverse tail fibers – may inspire artists, animators, and educators."
Dr Hodgkinson-Bean says understanding the structure of the viruses also aids understanding of their evolution.
"While DNA generally serves as the best evolutionary marker in humans, the 3-dimensional structure of a virus is more informative of its distant evolutionary relationships with other viruses," he says.
They study found features only previously found in very distantly related viruses, revealing previously unknown evolutionary links between them.
"We know through structural studies that bacteriophages are related to Herpes viruses – this relationship is thought to extend back billions of years to before the emergence of multi-cellular life. For this reason, when we look at bacteriophage structure, we are looking at living fossils, primordial ancient beings.
"There is something truly beautiful about that."
Significantly, this structure is the second of its kind described by the same group of researchers, following a previous study on pathogens which cause diseases in potatoes, recently published in Nature Communications.
Publication:
Cryo-EM Structure of Bacteriophage Bas63 Reveals Structural Conservation and Diversity in the Felixounavirus genus
James Hodgkinson-Bean, Rafael Ayala, Klemens McJarrow-Keller, Léna Cassin, Georgia L. Rutter, Alexander J.M. Crowe, Matthias Wolf, Mihnea Bostina
Science Advances
