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Wake Up and Die: Activating Dormant Bacteria to Kill Them

A new strategy for wiping out quiescent infections could help to battle tuberculosis and other infectious diseases
e. coli culture



© ISTOCKPHOTO/LINDE STEWART

Israeli researchers announced this week that they have developed a new technique that may wipe out stubborn bacteria that elude antibiotics. Some infections such as tuberculosis (TB) can lay dormant in the lungs for decades before reactivating and causing symptoms— even after most of the disease-causing bacteria have been leveled by antibiotics.

But scientists at The Hebrew University of Jerusalem report in Proceedings of the National Academy of Sciences USA that they discovered a way to eradicate the stubborn bugs and prevent them from suddenly striking again when an individual's immune system is off guard. The new method capitalizes on the dormant bacteria's need for nutrients such as iron and magnesium. Such cells can avoid antibiotics when they're starved and become inactive. But the researchers were able to reduce populations of persistent bacteria by up to 99 percent by first perking them up with nutrients and then blasting them with an antibiotic.

For their study, the team flooded a line of Escherichia coli (a common bacterium that lives harmlessly in the intestinal tracts of many animals, although some strains can cause food poisoning with antibiotics, killing some of cells but leaving behind a gaggle of stubborn ones. When researchers infused the survivors with nutrients (including a carbon source, iron and magnesium), they seemed to awaken from a dormant state for about an hour, but did not replicate as normal bacteria would; when the researchers gave them nutrients, plus a dollop of antibiotics, they were reinvigorated but soon died.

"Usually when you stop giving nutrients to any bacteria that you study, you wait a couple of hours for them to adapt and that's when you start putting on antibiotics," says study co-author Nathalie Balaban, a biological physicist. "When we exposed them to fresh nutrients and antibiotics at the same time, we were able to reduce their numbers by an order of magnitude." She estimates that her team eradicated 99 percent of the bacterial population.

Kim Lewis, director of Northeastern University's Antimicrobial Center, said the new work is interesting, but that more research is needed. He noted that the strain of E. coli that the Hebrew University team used in its experiments is a mutant strain that is known to leave a higher number of persisters than the normal type of the bacteria. He says the variation may skew the results if applied to other types of bacteria.

Balaban agrees that the technique must be tested in animals to gauge its effectiveness in the body (as opposed to the less complex environment of a cell culture). She anticipates some challenges including the accessibility to infection sites. In the case of a urinary tract infection, for instance, she notes that it would be relatively easy to flush the bladder and the rest of the urinary tract. But it could be harder to reach bacteria in the case of respiratory infections such as TB—and figure out what to feed them to get them to wake up and drink in antibiotic.

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