Exploding bacteria
Microbiologists have discovered that the superbug Pseudomonas aeruginosa causes infection in a most unusual way — by blowing itself up.
P. aeruginosa infections present a growing risk in hospitals, where people with compromised immune systems are vulnerable to infection. The multidrug-resistant superbug survives in biofilms — groups of cells or microorganisms that stick to each other and adhere to a surface.
Associate Professor Cynthia Whitchurch and Dr Lynne Turnbull, from the ithree institute at the University of Technology Sydney (UTS), have spent years researching P. aeruginosa to understand how bacteria release virulence factors such as DNA, proteins and membrane vesicles (MVs) into their environment. Once released, the contents are used by the remaining bacteria as a ‘glue’ to build the biofilm, as a food source and as virulence factors that contribute to the infection process.
“We originally thought the extracellular DNA (an important biofilm component) might have been produced through a process where the cells die and slowly leak out their genomic DNA,” said Dr Turnbull. “But by using a special stain that lights up fluorescently when it detects extracellular DNA, we saw cells that were exploding like starbursts or fireworks of DNA.”
Dr Turnbull said the Pseudomonas cells undergo an incredible transformation before exploding, with the whole process taking place in as little as six seconds.
“The normal bacteria look like little rods or pills,” she said. “One day, as we looked under the microscope, we saw one of the cells turn from a hard, structured rod into a round, soft ball. Within a few more seconds, it then violently exploded. It’s amazing how quickly it happens and is likely the reason it hasn’t been observed before.”
The researchers looked to bacteriophage — viruses that infect bacteria — and identified a gene specifically involved in the process of P. aeruginosa cells rounding up and exploding. They then used a sophisticated microscope, the DeltaVision OMX Blaze from GE Healthcare, to see exactly what happens after a bacterium explodes.
“The explosive cell lysis of a sub-population of cells accounts for the liberation of cytosolic content in Pseudomonas aeruginosa biofilms,” the researchers wrote in the journal Nature Communications. “Super-resolution microscopy reveals that explosive cell lysis also produces shattered membrane fragments that rapidly form MVs.”
The researchers will now turn their attention to understanding the specific role of exploding cells in infection. They predict it will be important not only in biofilm infections, but also in tackling the global problem of antibiotic resistance.
“We think there will be a two-pronged approach: one is to prevent the biofilms being produced by stopping bacterial explosions, but if we can’t prevent it, then the second approach will be to induce the process that causes the bacteria to explode, so they all die en masse, causing the infection to clear,” Associate Professor Whitchurch said.
“We know we can induce this explosive cell death pathway through antibiotic treatment, so maybe we can use this to kill whole populations of bacteria — it’s a potential therapy. We know certain classes of antibiotics can induce this pathway; however, now that we know about how cells explode, we have an opportunity to directly target that process more specifically, perhaps with new types of antibiotics or by finding drugs or chemicals that cause this process to be turned on.”
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