This Time-lapse Video Will Reveal How Bacteria Evolves And Develops Resistance

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If seeing is believing, then it doesn’t get better than this!

Scientists from Harvard Medical School and Technion-Israel Institute of Technology have designed a simple and effective way to observe the evolution of bacteria into superbugs! By the end of the experiment, they managed to create a bacteria that is 1000 times more drug-resistant than their ancestors.

Credit: Harvard medical school video screenshot
Credit: Harvard medical school video screenshot

In this time-lapsed video, scientists tracked a mega-sized, 2-by-4-foot petri dish filled with 14 litres of agar. To observe how the bacterium E.coli adapts to the increasing dose of antibiotics, they divided the dish into sections and saturated them with varying concentrations of the antibiotic. The periphery of the dish contained no antibiotics and every subsequent section towards the centre contained a 10-fold increase in concentration until the centre of the dish where the antibiotics concentration was 1000 times more than the initial band.

Over the span of two weeks, an overhead camera took periodic snapshots of the dish that was stitched together to make a time-lapse video. What resulted was a powerful way to visualise the growth of bacteria when conditions were unfavourable and how it adapted, evolved and continued to grow, all 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 and adapt or die, the researchers said. Says senior study investigator Roy Kishony,

 Seeing the bacteria spread for the first time was a thrill. Our MEGA-plate takes complex, often obscure, concepts in evolution, such as mutation selection, lineages, parallel evolution and clonal interference, and provides a visual seeing-is-believing demonstration of these otherwise vague ideas. It’s also a powerful illustration of how easy it is for bacteria to become resistant to antibiotics.

“This is a stunning demonstration of how quickly microbes evolve,” said co-investigator Tami Lieberman.

“When shown the video, evolutionary biologists immediately recognize concepts they’ve thought about in the abstract, while nonspecialists immediately begin to ask really good questions.”

Some of the key observations from the study were as follows:

  • Initial growth of the bacteria was dictated by the concentration of the antibiotic. Bacteria spread until they reached a concentration (antibiotic dose) in which they could no longer grow.
  • At each level of the concentration gradient, a small group of bacteria adapted and survived. While progressing through the different concentrations of the antibiotics, the bacteria accumulated genetic changes. As drug-resistant mutants arose, their successive generations migrated to areas of higher antibiotic concentration. They progressed until they reached a drug concentration at which they could not survive.
  • As the bacteria progressed through higher doses of the antibiotic trimethoprim, low-resistance mutants gave rise to moderately resistant mutants, eventually giving rise to highly resistant strains able to fend off the highest doses of antibiotic.
  • In a span of 10 days, the bacteria produced mutant strains that would withstand antibiotic doses 1000 times higher than the one, that killed their progenitors. When researchers used another antibiotic—ciprofloxacin—bacteria developed 100,000-fold resistance to the initial dose.
  • Initial mutations led to slower growth—a finding that suggests bacteria adapting to the antibiotic aren’t able to grow at optimal speed while developing mutations. Once fully resistant, such bacteria regained normal growth rates.
  • The fittest, most resistant mutants were not always the fastest. They sometimes stayed behind weaker strains that braved the frontlines of higher antibiotic doses.

What we saw suggests that evolution is not always led by the most resistant mutants,” Baym said. “Sometimes it favours the first to get there. The strongest mutants are, in fact, often moving behind more vulnerable strains. Who gets there first may be predicated on proximity rather than mutation strength.

As useful as this technique proves to be, the most interesting part was how this technique came into existence! In a bid to teach evolution in a visually captivating way to students, senior investigator Roy Kishony adapted this idea from a digital billboard advertisement he saw of the 2011 Hollywood film Contagion. In the advertisement, a giant lab dish was shown, with glowing microbes slowly creeping across a dark backdrop to spell out the title of the movie!

A case of Hollywood inspiring scientists? Well, we are not complaining!

Source: Harvard Medical School

Original Paper: Science