Infective explosions

Extracellular DNA (yellow) is released by exploding bacteria in biofilms of the bacterial pathogen Pseudomonas aeruginosa (blue). Image by E. Gloag and L. Turnbull, UTS ithree institute
13 April 2016

Published in Nature Communications: An international team of microbiologists led by scientists at the University of Technology Sydney (UTS) found that Pseudomonas aeruginosa cells explode violently for the good of their community. The discovery helps to explain how the bacteria cause infections with potentially deadly consequences. It may also play a role in developing ways to prevent and treat superbug infections.

Multi-drug resistant forms of Pseudomonas aeruginosa present a growing risk in hospitals where people with compromised immune systems, such as the elderly, newborns and surgical and cancer patients, are vulnerable to infection.

These 'superbugs' survive in so called biofilms - groups of cells or microorganisms that stick to each other and adhere to a surface.

An important part of the process that leads to biofilms is that some bacteria die and release virulence factors such as DNA, proteins and membrane vesicles into their environment. They provide a food source for remaining bacteria, and include virulence factors that contribute to the infection process.

Notably, extracellular DNA from dead bacteria is used as a 'glue' to build the biofilms.

Previously it was thought that the DNA was produced by bacteria dying and slowly releasing genomic DNA into the environment.

However, by using a fluorescent stain that detects extracellular DNA, the researchers revealed starbursts or fireworks of DNA that were produced by exploding P. aeruginosa bacteria.

Normal P. aeruginosa bacteria look like little rods or pills. But the researchers found that some cells turn from a hard, structured rod into a round, soft ball, and within a few seconds they violently explode.

Using super-resolution microscopy*, the researchers also found that the exploding bacteria produce shattered membrane fragments that rapidly form vesicles. Together with the extracellular DNA, these membrane vesicles form part of the biofilm matrix.

To understand why the cells explode, the researchers examined the presence of bacteriophage – viruses that infect bacteria and have been been linked with rapid bacterial cell death. They found a bacteriophage gene specifically involved in the process of Pseudomonas aeruginosa cells rounding up and exploding. Mutants of P. aeruginosa that don't have this gene don’t explode and, more importantly, don’t build biofilms.

This surprising finding suggests that P. aeruginosa actually benefits from continuous viral infections, as it provides a mechanism for bacteria to explode and efficiently release internal content for use by the remaining members of their community.

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.

According to lead investigator Associate Professor Cynthia Whitchurch, there could be a two pronged approach: preventing the biofilms being produced by stopping bacterial explosions, and if this is not successful, inducing the bacteria to explode en masse to clear the infection.

“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.”

Story based on a media relelease from the University of Technology, Sydney *Super-resolution microscopy was done with the DeltaVision OMX Blaze™ from US firm Applied Precision.