Unexpected beauty and major antimicrobial power increase as phages transform into surprising flower shapes

A group of McMaster researchers who regularly work with bacteriophages – viruses that eat bacteria – got a pleasant and potentially very important surprise when they prepared slides for viewing under a powerful microscope.

After processing samples of what are informally called phages so that they could be observed alive under an electron microscope, the researchers were surprised to find that they had come together to form three-dimensional shapes that resemble sunflowers. , but with a diameter of only two tenths of a millimeter.

With a little prodding, nature has engineered the very type of structure that experts in their field have been trying to construct artificially for decades – one that is 100 times more effective than unrelated phages at finding elusive bacterial targets.

Being able to create such structures opens possibilities for the detection and treatment of many forms of disease, all using natural materials and processes, the researchers say.

Their work is explained in an article recently published in the journal Advanced functional materials.

The initial discovery was a happy accident resulting from daily laboratory work.

Rather than exposing the phage samples to typical preparation processes, which involve temperatures or solvents that kill viruses, lead author Lei Tian and colleagues chose to treat them with high-pressure carbon dioxide. . Tian, ​​now a senior researcher at Southeast University in China, led the research while he was a doctoral student. student and later postdoctoral researcher at McMaster.

While the researchers are used to seeing microscopic viruses do amazing things, after treatment they were stunned to find that the phages had grouped together into such complex, natural and very useful forms.

“We were trying to protect the structure of this beneficial virus,” Tian explains. “That was the technical challenge we were trying to overcome. What we got was this amazing structure, created by nature itself.”

The researchers captured images of the formations using facilities at the Canadian Center for Electron Microscopy, located at McMaster, and have spent the past two years unlocking the process and showing how the new structures can serve very useful purposes in science. and in medicine.

“It was an accidental discovery,” says the paper’s corresponding author, Tohid Didar, a mechanical engineer and Canada Research Chair in Nanobiomaterials. “When we took them out of the high pressure chamber and saw these beautiful flowers, it completely blew us away. It took us two years to discover how and why this happened and opened the door to the possibility of create similar structures with other protein-based materials.”

In recent years, researchers in the laboratory of lead author Zeinab Hosseinidost, a chemical and biomedical engineer who holds the Canada Research Chair in Bacteriophage Bioengineering, have made significant advances in phage research by enabling beneficial viruses to connect together like a living, microscopic tissue, and even to form a gel visible to the naked eye, thus opening new perspectives for their application, particularly in the detection and fight against infections.

But before the most recent discovery, it was not possible to give the material the shape and depth it has today through the wrinkles, peaks and crevices of the flower-shaped structures.

“It’s really about building with nature,” Hosseinidost says. “This type of beautiful, wrinkled structure is ubiquitous in nature. The mechanical, optical, and biological properties of this type of structure have inspired engineers for decades to artificially build these types of structures, hoping to achieve the same type of properties.

Now that they have triggered such a transformation and succeeded in replicating the process, researchers marvel at the collective efficiency phages achieve by uniting and assuming such forms, and they are exploring ways to use the same properties.

The porous flower-like structures of phages are 100 times better than their unbound counterparts at finding dispersed and diffuse targets, even in complex environments, a fact the authors were able to prove by mixing them with DNAzymes created by their colleagues of infectious disease research and using the flower-like formations to find low concentrations of Legionella bacteria in commercial cooling tower water.

Bacteriophages are re-emerging as treatments for many forms of infection because they can be programmed to target specific bacteria while leaving others alone.

Work in this area ceased after the introduction of penicillin in the middle of the last century, but as antimicrobial resistance continues to erode the effectiveness of existing antibiotics, engineers and scientists, including McMaster researchers , turn their attention to phages.

Discovering the process that causes them to bind together into flower shapes may enhance their already impressive properties, both for finding and killing targeted bacteria, but also for serving as a scaffold for other beneficial microorganisms and materials.

“Nature is so powerful and so intelligent. As engineers, our job is to learn how it works, so we can harness processes like this and put them to good use,” says Hosseinidooust. “The possibilities are endless, because we can now create structures using biological building blocks.”