Scientists Find Way To Identify Antibiotic-Resistant Sleeper Cells That ‘Play Dead’ Before Wreaking Havoc

EXETER, England — In what sounds like a Stephen King plot line, certain antibiotic-resistant cells “play dead” only to return to life and begin replicating themselves after a period of dormancy. These “sleeper cells,” capable of surviving rounds of antibiotics before going into a death-like dormant phase, are helping researchers at the University of Exeter better understand antibiotic resistance.

Researchers there have discovered a new way to identify cells that are likely to survive antibiotic treatment, even before the drugs are administered. This knowledge may lead to improved ways to target and annihilate the little resisters.

Scientist looking into microscope
Researchers there have discovered a new way to identify cells that are likely to survive antibiotic treatment, even before the drugs are administered.

“Antibiotic resistance is one of the serious health challenges of our age,” says lead study author Dr. Stefano Pagliara, a biophysicist at the university, in a news release. “The cells we identified elude antibiotic treatment and pose a serious threat to human health. In fact, unlike persister cells which quickly resume growth after the antibiotic course ends, ‘sleeper cells’ remain non-growing for prolonged periods of time, and elude detection using traditional methods.”

All cells that survive antibiotic treatment can eventually begin dividing and causing re-infection. When this happens, antibiotic-resistant bacteria get a leg up. There are two types of cells that survive antibiotic treatments. The one that is a bigger problem, both in terms of number and detectability, is the sleeper cell. These cells, which make up the majority of survivors, give the distinct impression that they are goners when viewed by traditional methods.

The other type of survivor cell is the persister cell. They do not hide their intentions for long. Just as soon as the course of antibiotics ends, they are quickly back at work, redividing and reinfecting. Though easily detected by traditional methods, persister cells account for just a third of surviving bacteria cells. This presents a dilemma.

To solve this problem, researchers developed a miniaturized device that allows them to isolate and study single bacteria over time. The device, which uses fluorescence to light up individual cells, revealed that sleeper cells were not truly defeated, despite giving off the appearance of being dead or dying.

Remember, because they are non-growing, sleeper cells appear just like dead cells. When researchers dosed bacteria with ampicillin, they found that most of the 1.3 percent of bacterial cells that survived were live but non-growing. This would lead to the assumption that more bacteria were killed by the antibiotics than was actually the case. Instead, the sleeper cells would be lying in wait, ready to wake up and re-infect at some later date.

Researchers see similar features in both sleeper and persister cells that suggest a link between the two. Both have a unique fluorescence and can be spotted before the dose of antibiotics is even started. This might be the key to their undoing.

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Researchers aim to take their discoveries to the next level. Pagliara is planning a program to identify and isolate each sleeper cell. This will allow researchers to study next-generation sequencing to determine how these antibiotic resistant cells express genes differently from those who succumb to a round of antibiotics.

“Our research should make it easier to develop biomarkers to isolate these cells and open up new ways to map the biochemical makeup of bacteria that can escape antibiotics,” says Pagliara, “so we can find ways of targeting them effectively.”

The research was published in the Dec. 21, 2017 edition of the journal BMC Biology.

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