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The Garden of Eartly Delights

Finger Machines

This time-lapse is a compelling, and unsettling, visualization of evolution.

The overhead footage depicts a strain of the gut bacterium 'E. coli' evolving to 1,000 times more resistant to an antibiotic in only 11 days... Showing just how fast diseases can adapt to the drugs that we throw at them...

*The demonstration plays out on a giant petri dish called the 'Microbial Evolution and Growth Arena plate' or 'MEGA-plate'

Beyond providing a telegenic way to show evolution, the device yielded some key insights about the behavior of bacteria exposed to increasing doses of a drug. Some of them are:

*Bacteria spread until they reached a concentration (antibiotic dose) in which they could no longer grow

*At each concentration level, a small group of bacteria adapted and survived. Resistance occurred through the successive accumulation of genetic changes. As drug-resistant mutants arose, their descendants migrated to areas of higher antibiotic concentration. Multiple lineages of mutants competed for the same space. The winning strains progressed to the area with the higher drug dose, until they reached a drug concentration at which they could not survive.

*Progressing sequentially through increasingly higher doses of antibiotic, low-resistance mutants gave rise to moderately resistant mutants, eventually spawning highly resistant strains able to fend off the highest doses of antibiotic.

*Ultimately, in a dramatic demonstration of acquired drug resistance, bacteria spread to the highest drug concentration. In the span of 10 days, bacteria produced mutant strains capable of surviving a dose of the antibiotic trimethoprim 1,000 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.

The classic assumption has been that mutants that survive the highest concentration are the most resistant, but the team’s observations suggest otherwise..

“What we saw suggests that evolution is not always led by the most resistant mutants,” Baym said. “Sometimes it favors 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.”

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