Incredible time-lapse footage reveals the path of bacteria as they grow to be ‘superbugs,’ ultimately thriving in the antibiotics meant to kill them.

To capture these remarkable observations, researchers constructed a giant petri dish and recorded the progression of E. coli exposed to various doses of medication.

This breakthrough is thought to be the first large-scale glimpse of these processes, showing evolution at work as bacteria adapt to increasingly high doses of antibiotics.

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The footage shows evolution at work as bacteria adapt to increasingly high doses of antibiotics. As seen above, the bacteria quickly evolved resistance to extremely high concentrations of the medication

THE SUPERBUG PROBLEM Antibiotic-resistant bacteria such as Salmonella, E. Coli and Staphylococcus infect some 2 million people and kill at least 23,000 people in the United States each year. Efforts to thwart these so-called 'superbugs' have consistently fallen short due to the bacteria's ability to rapidly adapt and develop immunity to common antibiotics such as penicillin. Advertisement

Scientists from Harvard Medical School and Technion-Israel Institute of Technology constructed a 2-by-4 foot petri dish to study the adaptations of Escherichia coli (E. coli) over the course of two weeks.

Their findings are discussed in a paper published today in the journal Science.

The team split the giant dish into sections of varying dosage to create a device dubbed the Microbial Evolution and Growth Arena (MEGA) plate, inspired by the 2011 film Contagion.

Those on the outermost rim were free of any drug, while the next level contained just enough antibiotic to kill the bacteria.

And, in each subsequent section, the dose increased 10-fold, with 1,000 times as much antibiotic at the center than in the areas with the lowest dose.

Then, the researchers attached a camera to the ceiling and periodically photographed the progression during the two week period.

The team split the giant dish into sections of varying dosage to create a device dubbed the Microbial Evolution and Growth Arena (MEGA) plate, inspired by the 2011 film Contagion. In each subsequent section, the dose increased 10-fold, as illustrated above

This method allowed them to observe the relationship between physical space and evolutionary challenges that lead to adaptation.

‘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 Michael Baym, a research fellow in systems biology at HMS and lead author of the study.

By examining the bacteria in this way, the researchers noted numerous key insights on their behaviour in response to increasing doses of antibiotics.

And, the observations challenge standard assumptions that mutants which survive the highest doses are the most resistant.

WHAT THEY FOUND The researchers also found that the mutants produced successors of higher resistance as they progressed to higher doses, with the most resistant version able to fight the highest dose. In just 10 days, the mutant strains were able to survive an antibiotic (trimethoprim) 1,000 times higher than that which killed their predecessors. And when they switched to the antibiotic ciprofloxacin, the bacteria became resistant 100,000 times that seen in the initial dose. The observations suggest that bacteria grow more slowly when adapting to antibiotics; once they’ve become fully resistant, their growth rate returned to normal. And, the most resistant mutants often moved more slowly than weaker strains, staying behind as others first encountered the higher doses Advertisement

‘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,’ said Roy Kishony of Harvard and Technion, senior study investigator.

‘It’s also a powerful illustration of how easy it is for bacteria to become resistant to antibiotics.’

Among their many observations, the researchers found that the bacteria spread until they hit a dosage upper-limit, in which the concentration of the antibiotic becomes so high that they cannot grow.

A small group of bacteria was found to adapt and survive at each level, and resistance occurred through successive genetic changes.

The researchers attached a camera to the ceiling and periodically photographed the progression during the two week period

When drug-resistant mutants came about, the descendants moved to areas of higher concentration, and multiple lineages of the mutants competed for the same space

Those which out-competed the other strains continued on to higher doses until they hit a point at which they could not survive

When drug-resistant mutants came about, the descendants moved to areas of higher concentration, and multiple lineages of the mutants competed for the same space.

Those which out-competed the other strains continued on to higher doses until they hit a point at which they could not survive.

‘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.’

The researchers also found that the mutants produced successors of higher resistance as they progressed to higher doses, with the most resistant version able to fight the highest dose.

A small group of bacteria was found to adapt and survive at each level, and resistance occurred through successive genetic changes. And, the most resistant mutants often moved more slowly than weaker strains, staying behind as others first encountered the higher doses

In just 10 days, the mutant strains were able to survive an antibiotic (trimethoprim) 1,000 times higher than that which killed their predecessors.

And when they switched to the antibiotic ciprofloxacin, the bacteria became resistant 100,000 times that seen in the initial dose.

The observations suggest that bacteria grow more slowly when adapting to antibiotics; once they’ve become fully resistant, their growth rate returned to normal.

And, the most resistant mutants often moved more slowly than weaker strains, staying behind as others first encountered the higher doses.

‘What we saw suggests that evolution is not always led by the most resistant mutants,’ Baym said.