Bacteria in the human body thrive in 3D structured communities, so studying pathogens in this type of environment could better show how they interact. Now, scientists are doing just that – with microscopic 3D printed cages.

Scientists from the University of Texas at Austin have used a new 3D printing technology, which allowed them to construct homes for the bacteria at a micro level.

By encasing bacteria in these tiny homes, they were able to study how bacteria found in the human gut and lungs collaborate to develop infections.

A study of their work was published in the journal Proceedings of the National Academy of Sciences.

To construct the cages, which are made of protein, the researchers used a laser and built the cages around bacteria in gelatin. The cages can be almost any shape or size, say the researchers, and they can be moved around other cages that contain other bacteria communities.

In an experiment, they were able to show how a community of bacteria that causes skin infections, Staphylococcus aureus, became more antibiotic-resistant when it was in a cage with a community of another bacteria involved in cystic fibrosis, Pseudomonas aeruginosa.

The researchers say this new method they employed should allow future studies to recreate better conditions – more like the human body – in which bacteria thrive.

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This 3D skull was printed in the same way the bacterial cages are – layer by layer. Credit: Jason Shear

The gelatin in which the bacteria is encased is quite flexible, say the researchers. A liquid solution when warm, it can also become firm at room temperature.

It also contains photosensitive molecules, which prompt the gelatin molecules to react with each other when hit with a laser light.

After the researchers decide which bacteria they want to encase and in which shape, they activate the laser, forming a solid matrix.

Jason Shear, professor of chemistry at the University of Austin, explains further:

“Then we do another layer, and another, and so on, building up. It’s very simple. We’re basically making pictures and stacking them up into 3D structures, but with incredible control.”

“Think about the thickness of a hair on your head, and take 1% of that, and then take about a quarter of that. That’s about the size of our laser when it’s brought to its smallest point.”

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The 3D printed cages (red) can be any shape or size, and they can be moved close to other structures with different bacterial communities (green). Credit: Jason Shear

Once the cages are completed, the researchers feed the bacteria nutrients to encourage them to reproduce within the space provided. The researchers can then take other caged communities and put them within a close distance so they can signal to each other.

Additionally, the researchers have the capability to wash away the gelatin, stop the bacterial growth and store them for transport.

Prof. Shear says the structures do not allow the bacteria to escape, but “they are porous enough to be chemically permissive,” meaning that signals can be exchanged.

He says the new technique provides new opportunities to study bacterial growth. For example, bacteria such as Staph and Pseudomonas can be arranged together to see how they react when they are both presented with an intruder.

Prof. Shear adds:

These are really common bacteria that are often found together in infections, and it makes sense that they would have mechanisms to sense each other. What the technology allows us to do is put them in conversation with each other, in very precise ways, and see what happens. In this case the Staph sensed the Pseudomonas, and one result was that it became more resistant to the antibiotics.”

Prof. Shear says that their technique can be used to study how infections spread, for example in a hospital, where avoiding infections is key.

He points to previous studies that suggest infections are transmitted by tiny colonies of bacteria that travel on equipment or staff, and that are therefore wide-reaching throughout a hospital.

By studying how bacterial communities work together, he believes other questions can be addressed:

We currently know little about how this is happening. How many cells does it take? Do these microcommunities become particularly virulent or antibiotic resistant precisely because they’re small, and then in turn change the properties of bacteria on our skin or in our bodies? Now we have a means to start asking these questions much more broadly.”

These findings are particularly timely, as the Centers for Disease Control and Prevention (CDC) has recently called for action against drug-resistant bacteria.