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A group of scientists were surprised recently when they trained a powerful new microscope on a colony of dangerous drug-resistant bacteria responsible for thousands of hospital-acquired infections and hundreds of deaths in the U.S. alone annually. They watched microbes from the family Pseudomonas aeruginosa blow themselves up and rain the contents of their cells on their nearby kin. The ejecta contained bits of cellular membrane, DNA, carbohydrates, proteins and other raw materials that the colony used like Lego blocks to grow the slimy biofilm that protected and nourished them.
“The normal bacteria look like little rods or pills,” said Lynne Turnbull, a microbiologist at Australia’s University of Technology Sydney who was involved in the research. “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.”
Cynthia Whitchurch, another UTS microbiologist and a lead investigator on the project, explained what the group saw. “When most people think about bacterial cell death, they think of cells dying and their contents slowly leaking out, similar to what you would see with a piece of fruit rotting,” she explained. “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.”
Top image: Extracellular DNA (yellow) is released by exploding bacteria in biofilms of the bacterial pathogen P. aeruginosa (blue). Image by E. Gloag and L. Turnbull, UTS ithree institute
Scientists call this behavior explosive cell lysis. It releases shards of the cell’s membrane and DNA into the surrounding environment in as little as six seconds. In a paper published in April in the journal Nature Communications, the international team of scientists revealed that the fragments re-form into little bubbles called membrane vesicles, which help the remaining cells reinforce the tough biofilm matrix that serves as their scaffolding and armor.
“This was completely unexpected, as until now bacterial membrane vesicles were thought to form from membranous protrusions at the cell surface,” said study co-author Masanori Toyofuku, a microbiologist with the University of Tsukuba and University of Zurich.
Because explosive lysis happens so quickly — in a matter of seconds — researchers needed special microscopy equipment to catch it. They first used a special stain that glows when it is in the presence of DNA outside the cellular membrane.
Then they peered through an instrument called a GE DeltaVision OMX super-resolution microscope, which let them see objects two times smaller than what traditional microscopes allow. (It’s so powerful that some researchers call it the “OMG microscope.”) They were able to catch members of the rod-shaped P. aeruginosa colony squish down into spheres before blowing up, revealing fluorescing DNA “like starbursts or fireworks,” said UTS’s Turnbull.
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A photograph of a dividing cell taken with the OMX microscope taken by Indiana University researcher Jane Stout.
Here’s what’s interesting. The study found that only a few members of a colony of P. aeruginosa trigger their own premature demise. The rest progress through the microbe’s normal life cycle.
The scientist also saw an uptick in these cellular suicides when the colony came under pressure, like when they came into contact with potentially deadly antibiotics. For that reason, the team believes that explosive lysis is a survival mechanism that is key to the colony’s well-being. It’s a case of a few sacrificing themselves to provide a communal good — the raw materials needed for the majority’s survival.
The exploded microbes’ liberated guts help form the biofilm that allows the surviving colony members to grow on hospital equipment and medical supplies like catheters. This then puts patients at risk for infection when they come into contact with the virulent organisms.
The discovery could open new paths to fight the menace of antibiotic-resistant bugs. The first is finding a way to prevent bacterial cells from undergoing explosive lysis and stopping them from providing the raw materials needed to produce biofilms. The second approach could be to figure out how to get all of the colony’s members to undergo explosive lysis, causing the whole population to die instead of just a few martyrs.
“This is really important work in the fight against a major public health crisis,” said Kimberly Collins, a biologist at GE Healthcare who is familiar with the team’s research. “And it is something that couldn’t have been done not too long ago. Fast imaging of living cells made this discovery possible.”