In our midsts lurk
superbugs, bacteria that cannot be killed by the most potent drugs for treating antibiotic infections. The pathogens come with the kind of long, italicized names that send chills down your spine: Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus, Clostridium difficile and Shiga toxin-producing E. coli.
Researchers from Harvard Medical School and Technion-Israel Institute of Technology, who study these organisms, wanted to show their students just how tenacious the bacteria were. So they set up a big, antibiotic-laced Petri dish for millions of
Escherichia coli to swim through, and then aimed an overhead time-lapse camera on them to record how they would fare.
The results could help scientists better understand these deadly organisms and develop ways to fight them.
“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,” Michael Baym, a research fellow in systems biology at HMS, said in a
The Petri dish Baym and his colleagues built was gigantic: four feet long by two feet wide. They dubbed it the Microbial Evolution and Growth Arena or MEGA plate for short. Next, they filled it with agar, a clear, jellylike substance commonly used in labs to grow organisms.
They divided the MEGA plate into nine sections and then infused each section with a different dose of antibiotic drug. For example, on the two outer sections, they put no antibiotic drug, but in the next sections in, they put 1 times the amount and in the next sections, they put 10 times the amount. In the center section, they put 1,000 times the dose. See the illustration below.
Harvard Medical School
Over the top of the thick agar, they poured a thin layer of agar in which the bacteria could move around in. The bacteria began their lives at the far edges of the dish, where no antibiotic drugs existed. As they fed on the agar, the bacteria grew and multiplied and advanced toward the next section. Here, their growth stopped abruptly as many of them died after consuming the small dose of antibiotics.
It didn’t take long, however, for several to develop a mutation, and the video shows a small colony blooming and surviving in spite of the drugs.
“When the mutants hit the next boundary, they too have to pause and develop new mutations to make it into 10 times as much antibiotic,” the narrator of the video says.
Different mutants repeat the process when they encounter the agar containing 100 times the amount of antibiotic.
It took just 11 days for the bacteria to evolve to a state where it could survive in the agar that contained 1,000 times the dose of the original amount of antibiotic drug.
In another experiment, the researchers used a different antibiotic — ciprofloxacin — and found bacteria developing a 100,000-fold resistance.
“This is a stunning demonstration of how quickly microbes evolve,” said co-investigator Tami Lieberman in a
Among several findings, the researchers discovered that not all mutants were created equal. Those that survived at the highest rate weren’t necessarily the most resistant.
“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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