By Jerry Grillo

It’s the quiet bacteria that you’ve got to watch out for, the bacteria that can survive antibiotic treatments by forming dormant, drug-tolerant “persisters.” These persister bacteria can wake up after treatment and prolong infections.

Persisters were first described about 80 years ago in some of the first studies of the antibiotic penicillin. Later, it was discovered that these bacteria didn’t have genetic resistance to antibiotics – they basically go dormant, hibernating, essentially hiding from the treatment that has been designed to kill them. 

How they wake up again has remained a mystery. But researchers with the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University are working to solve it. Along the way they’ve developed a better understanding of how bacteria can resist the therapeutic power of antibiotics, which could lead to more effective treatments down the road.

“These persisters don’t have the genes that can inactivate an antibiotic, but they still survive treatment,” said Kyle Allison, whose lab recently published its work in the journal Molecular Systems Biology. In fact, their study made the cover of the print edition published this month.

“Persisters are thought to play a role in a lot of different kinds of chronic infections,” Allison said. “We approached them like an engineering problem. Rather than trying to invent or discover a brand-new antibiotic, perhaps all we need to do is understand why these bacteria survive.”

Most studies of persisters focus on figuring out how they form. But Allison reasoned that the therapeutically interesting question is: How do they wake up or resuscitate from their dormant state?

“It’s a challenge to study this because these are rare cells, and bacterial cells are very small, so they’re hard to track and it’s hard to monitor their behaviors,” said Allison. “So, we developed methods that can look at thousands of cells at high magnification over long periods of time. That enabled us to study resuscitation – the waking-up moment for these persister cells in a statistically rigorous way.”

Allison – whose partner in the study was lead author Xin Fang, a postdoc in his lab – said they expected the bacterial cells to wake up randomly, which would be consistent with past studies into the phenomenon. But the activity of individual persister bacteria cells had never been verified. Through their close inspection, using single-cell time-lapse microscopy, Allison and Fang noticed that persisters wake up at an accelerated rate after antibiotic treatment.