An international team of microbiologists led by scientists from University of Technology Sydney’s ithree institute have witnessed a previously unknown process - explosive cell death - that could help explain how a common nasty superbug becomes infectious.
The bacterium in question is called Pseudomonas aeruginosa; strains of these bacteria are a typical culprit of multiple-drug-resistant infections acquired in hospitals, often causing severe illness and even death.
When these bacteria congregate on a moist surface - for example, an open wound - they lump together into a slimy substance called a biofilm, which bacteria use for food and for spreading the infectious process. Such a biofilm is made up of freely floating bacterial DNA, RNA, proteins and the liquid contents that bacterial cells carry within.
Until now scientists weren’t sure about the processes involved in releasing all this material into the biofilm, but now high-resolution live cell microscopy has revealed something truly unexpected - the bacteria literally explode.
“We found that a subset of the [bacterial] population round up and explode quite dramatically, and in so doing they efficiently release all of their extracellular content, so that the rest of the bacteria are able to benefit from that shared resource," says Associate Professor Cynthia Whitchurch, lead author of the study published recently in Nature Communications.
"We were amazed at what we saw,” says Whitchurch. “What we thought we would see was that the whole population would be secreting a small amount of DNA, but to see this happen as a suicidal event for some of the bacteria was quite unexpected, actually."
The whole process - puffing up from a rod shape into a little ball and then bursting open - takes as little as six seconds: blink and you'll miss it. The researchers think this is likely one of the main reasons why no-one else has discovered these tiny explosions before.
“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,” says Dr Lynne Turnbull, co-author of the study at the ithree institute.
Researchers also looked into the mechanisms behind these explosions, and discovered that the bacteria have co-opted a gene from a virus that typically infects bacteria, causing rapid cell death. In a sense, they’re using the tool of an enemy for their own gain.
The incredibly high resolution of live microscopy they used allowed the researchers to see membrane vesicles released from the exploding bacteria. These vesicles - tiny molecular structures - shuttle around biochemicals as signals between the bacteria. They also play a role in manipulating the host's immune response, thus understanding how they end up outside the cells is a vital piece of information for the scientists.
"It actually gives us a couple of opportunities that we can exploit to try to develop new ways to prevent or treat infections,” says Whitchurch. “Now that we know that a percentage of the population will explode to release the public goods that the other bacteria can benefit from, it gives us an opportunity to actually stop that process."
Another approach would be to exploit the mechanism of explosion to cause bacterial death en masse once infection has already taken hold.
“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,” says Whitchurch.
According to Whitchurch, there are now further studies to be done - the scientists suspect that the mechanism they found in Pseudomonas cells could actually be really common, and preliminary investigations appear to confirm that.
"What we're now wanting to do is to investigate whether this whole process really does have a role in infection; that requires grant funding, which is the usual problem, of course." says Whitchurch.