Researchers exploring bacteriophages—viruses that infect bacteria—made an exciting and potentially significant finding while preparing samples for examination under an electron microscope. In a surprising twist, these phages formed three-dimensional arrangements resembling sunflowers, measuring just two-tenths of a millimeter in diameter, which enhances their efficiency by a factor of 100.
A team of researchers at McMaster University, who regularly study bacteriophages, encountered an unexpected yet crucial discovery while setting up slides for examination with a high-powered microscope.
After applying a special treatment to their phage samples for observation with an electron microscope, the team was astonished to see the phages naturally clustering into intricate three-dimensional structures akin to sunflowers, with a size of only two-tenths of a millimeter.
This formation was aided by a simple intervention from the researchers, resulting in a structure that has been sought after for decades by experts aiming to replicate it artificially; it significantly increases the efficiency of phages in targeting specific bacterial pathogens.
The ability to create such structures presents new opportunities for disease detection and treatment, utilizing natural materials and methods, according to the research team.
The findings are detailed in a newly published study in the journal Advanced Functional Materials.
This initial startling discovery arose during routine laboratory work.
Instead of using standard preparation techniques that could harm the viruses through heat or solvents, lead researcher Lei Tian and his team opted for a method involving high-pressure carbon dioxide. Tian, who is currently a principal investigator at Southeast University in China, conducted this research during his PhD and post-doctoral work at McMaster.
The researchers, accustomed to observing remarkable behavior from these viral particles, were nonetheless taken aback to find them combining in such intricate and beneficial configurations after treatment.
“We aimed to preserve the structure of this helpful virus,” Tian recounts. “Our goal was to overcome the technical challenge we faced, and what resulted was this incredible structure created by nature itself.”
The team captured images of these formations using the resources at the Canadian Centre for Electron Microscopy at McMaster, dedicating the past two years to understanding the process and demonstrating how these new structures can contribute valuable applications in science and healthcare.
In recent times, researchers led by senior author Zeinab Hosseinidoust, a chemical and biomedical engineer with a Canada Research Chair in Bacteriophage Bioengineering, have made considerable advancements in phage studies, enabling the beneficial viruses to link together like a living microscopic fabric, and even form a gel visible to the naked eye, broadening the scope of their application—especially in detecting and combating infections.
However, prior to this breakthrough, imparting shape and depth to the material had been unattainable, but now it exhibits the intricate characteristics of flower-like structures.
“This truly exemplifies working in harmony with nature,” Hosseinidoust explains. “Such beautifully wrinkled structures are prevalent in nature. The mechanical, optical, and biological properties of these formations have inspired engineers for decades to attempt artificial replication in hopes of achieving similar properties.”
With the successful initiation of this transformation and the ability to replicate the process, the researchers are fascinated by the enhanced efficiency achieved by the phages forming together in these ways, and they are investigating potential applications of these properties.
The porous, flower-like phage formations excel at locating dispersed and challenging targets in complicated environments—being 100 times more effective than unlinked phages—a fact the authors confirmed by combining them with DNAzymes developed by their colleagues in infectious disease research to identify low levels of Legionella bacteria in water from commercial cooling systems.
Bacteriophages are gaining attention as potential treatments for a variety of infections due to their ability to be programmed to specifically target certain bacteria while leaving others unaffected.
Interest in this field waned after penicillin became popular in the mid-20th century; but as antimicrobial resistance becomes a pressing issue, scientists and engineers, including those at McMaster, are turning their focus back to phages.
The newly discovered process that encourages phages to intertwine into flower shapes enhances their capabilities in targeting and eliminating specific bacteria while also providing a framework for other beneficial microorganisms and materials.
“Nature is remarkably powerful and intelligent. Our role as engineers is to comprehend these processes, harness them, and apply them effectively,” states Hosseinidoust.
“The potential is limitless now that we can construct these structures using biological building blocks.”
