In a creative stroke inspired by Hollywood wizardry, scientists from Harvard Medical School and Technion-Israel Institute of Technology have designed a simple way to observe how bacteria move as they become impervious to drugs.
The experiments, described in the Sept. 9 issue of Science, are thought to provide the first large-scale glimpse of the maneuvers of bacteria as they encounter increasingly higher doses of antibiotics and adapt to survive — and thrive — in them.
To do so, the team constructed a 2-by-4 foot petri dish and filled it with 14 liters of agar, a seaweed-derived jellylike substance commonly used in labs to nourish organisms as they grow.
To observe how the bacterium Escherichia coli adapted to increasingly higher doses of antibiotics, researchers divided the dish into sections and saturated them with various doses of medication. The outermost rims of the dish were free of any drug. The next section contained a small amount of antibiotic — just above the minimum needed to kill the bacteria — and each subsequent section represented a 10-fold increase in dose, with the center of the dish containing 1,000 times as much antibiotic as the area with the lowest dose.
Over two weeks, a camera mounted on the ceiling above the dish took periodic snapshots that the researchers spliced into a time-lapsed montage. The result? A powerful, unvarnished visualization of bacterial movement, death, and survival; evolution at work, visible to the naked eye.
The device, dubbed the Microbial Evolution, and Growth Arena (MEGA) plate, represents a simple, and more realistic, platform to explore the interplay between space and evolutionary challenges that force organisms to change or die, the researchers said.
“We know quite a bit about the internal defense mechanisms bacteria use to evade antibiotics, but we don’t really know much about their physical movements across space as they adapt to survive in different environments,” said study first author Michael Baym, a research fellow in systems biology at HMS.
The researchers caution that their giant petri dish is not intended to perfectly mirror how bacteria adapt and thrive in the real world and in hospital settings, but it does mimic the real-world environments bacteria encounter more closely than traditional lab cultures can. This is because, the researchers say, in bacterial evolution, space, size, and geography matter. Moving across environments with varying antibiotic strengths poses a different challenge for organisms than they face in traditional lab experiments that involve tiny plates with homogeneously mixed doses of drugs.
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