Study reveals that bacteria are capable of shedding damage to endure antibiotic treatment.

It’s the sooty bacteria you have to watch out for, bacteria that can survive antibiotic treatment by forming dormant “inhibitors” that are drug-resistant. These contaminated bacteria can wake up after treatment and prolong the infection.

Percester was first described about 80 years ago in some of the first studies of the antibiotic penicillin. Later, it was discovered that these bacteria don’t have genetic resistance to antibiotics — they’re basically dormant, dormant, essentially hiding from the treatment that was designed to kill them.

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

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

“Percester is thought to play a role in many different types of chronic infections,” Allison said. “We approached them as an engineering problem. Rather than trying to invent or discover a completely new antibiotic, perhaps all we need to do is understand why these bacteria survive.”

Most studies of perseverants focus on finding out how they form. But Allison added that an interesting therapeutic question is: How do they wake up or recover from a lethargic state?

“It’s hard to study this because these are rare cells, and bacterial cells are very small, so it’s hard to track them and it’s hard to monitor their behavior,” Allison said. “Therefore, we have developed methods that can look at thousands of cells at high magnification over long periods of time. This has enabled us to study resuscitation – the moment of awakening of these persistent cells in a statistically accurate way.”

Allison — whose study partner was lead author Shen Fang, a postdoctoral researcher in his lab — said they expected the bacterial cells to wake up randomly, which is consistent with previous studies on this phenomenon. But the activity of persistent bacterial cells was not verified. On closer inspection, using single-cell microscopy, Allison and Fang note that perseverance wakes up at an accelerated rate after antibiotic treatment.

“This led to some interesting questions,” Allison said. “Did the antibiotic have an effect on the dormant inhibitors? They were thought to go into hibernation, oblivious to the antibiotic. But we saw that the antibiotic actually had an effect — the more antibiotics they got during treatment, the slower they would wake up again.” We were even able to show that there is some harm in the inhibitors from antibiotic treatment, and many inhibitors seem to actually ignore this harm.”

Basically, it looked as if some cultivators were actually sacrificing themselves, allowing the group to awaken and develop colonies. The intellectuals seem to be enabling them to survive through division – allowing some to die so that the rest can survive.

Researchers saw this behavior when they studied many different pathogens (Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and Klebsiella pneumoniae) that cause completely different types of infections and have different antibiotic tolerance mechanisms.

“The fact that they all have this cell division when they wake up after antibiotic treatment was very surprising,” Allison said. “It suggests the possibility that this non-genetic mechanism allows bacteria to survive in patients.”

Allison has been interested in the topic of antibiotic resistance since he was in graduate school. Although he can’t claim that this phenomenon of resuscitation is widespread among patients, the fact that the researchers observed it occurring in lab samples, and randomly selected patient samples, “is probably very important,” he said. “It strongly hints that this may be an important mechanism underlying treatment failure in bacteria that lack genetic resistance.”