Outsmarting the superbug
Researchers at the ithree institute have designed a unique computer vision program to precisely analyse thousands of individual bacterial cells, revealing never-before-seen characteristics that will enable better management of infectious diseases.
Michelle Gee (University of Melbourne)
Scott Wade (Swinburne University of Technology)
UTS Data Arena
DeltaVision OMX Blaze™
Australian Research Council
National Health and Medical Research Council
Pseudomonas aeruginosa — “superbug” bacteria — can be a killer in hospitals where people with compromised immune systems, such as the elderly, newborns, surgical and cancer patients, are vulnerable to infection.
The superbug bacteria are multi-drug resistant and the source of urinary tract infections caused by catheters, accounting for about 20 per cent of hospital-acquired infections.
Associate Professor Cynthia Whitchurch and her team at UTS’s ithree institute have discovered that it might be possible to stop the spread of this superbug without resorting to antibiotics.
Pseudomonas aeruginosa cells survive in what are known as biofilms; communities of cells or micro-organisms that stick to each other and adhere to a surface. Whitchurch and her team have worked out that when bacterial cells move about in the biofilm, they follow pathways reinforced by continual use.
“By understanding how bacteria migrate across surfaces, what we hope to do is come up with ways to stop them doing that. We’re hoping to avoid antibiotics by being smarter than the bacteria,” she says.
To do this, Whitchurch introduced furrows into the surface of silicone used in catheters, which successfully cut down the migration of bacteria by five times in laboratory trials.
To look at the movement of the bacteria in a radical way, Whitchurch also donned 3D glasses and used the UTS Data Arena. This large cylindrical screen is four metres high and 10 metres in diameter, and has six 3D-stereo video projectors, allowing researchers to visually immerse themselves in their data.
First, her team colour-coded all the bacterial cells and used BacFormatics, a unique computer vision program they’d developed that automatically segmented, tracked and analysed densely packed bacterial cells.
“We were able to really easily see the whole biofilm where cells were moving fast. That revealed behaviours that we really couldn’t have appreciated in any other way,” she says.
Whitchurch and her team have also discoveredthat Pseudomonas aeruginosa cells explode violently, explaining how this bacteria produce extra cellular DNA and other components required to build biofilms and cause infections.
Once the dying cell explodes, the remaining bacteria use its contents (which include the proteins and extracellular DNA) as a “glue” to build the biofilm, as a food source, and as virulence factors that contribute to the infection process, enabling the bacteria to cause infections.
“When most people think about bacterial cell death, they think of the cell dying and their contents slowly leaking out, similar to what you would see with a piece of fruit rotting,” says Whitchurch.
“What’s so amazing about this discovery is that we now know the bacteria have a process that enables them to actively explode, and therefore efficiently release all of their internal contents, making these available for use by the remaining members of their community.”
While Whitchurch’s team used a conventional microscope for their initial explosion findings, they used a more sophisticated microscope, the DeltaVision OMX Blaze™, to see what happened next.
They were surprised to see that these explosions produced membrane fragments that curled up into vesicles — tiny spheres of membrane containing DNA, proteins and other virulence factors. The team are now using this knowledge to combat bacterial infections from another innovative perspective.
Photographer (C Whitchurch): Joanne Saad