Persister bacteria travel an alternate path to antibiotic resistance

Researchers at Princeton  lead by Mark Brynildsen), an associate professor of chemical and biological engineering have identified a new, troubling path that some bacteria take toward resistance. This research focused on bacteria that they named persisters.  A persister bacterium is different from antibiotic-resistant bacteria. While most antibiotic-resistant bacteria have acquired genetic mutations that directly protect them against antibiotics, persisters do not possess such mutations.

 

They have a better chance of survival than resistant mutants, because of certain genes they switch on or off before, during or after antibiotic therapy. It seems that the line between the antibiotic-resistant bacteria and persister bacteria is not as clear as scientists previously thought.

 

The researchers found that some persisters were more likely than standard bacteria to produce offspring with the direct, genetic-mutation resistance to antibiotics. The researchers found the persisters’ offspring went on to exhibit resistance not only to the drug their forbearers had survived but also to completely different classes of antibiotics.

 

The researchers used Escherichia coli (E. coli), as a model. The researchers initially characterized how persisters recover from an antibiotic attack.

 

“Our study has demonstrated that persister bacteria can add substantially to the risk that antibiotic-resistant mutants will arise,” said Mark Brynildsen, the research lead. “We’ve known that because they survive the first wave of treatment, persisters can cause chronic infections. But their role in promoting drug resistance is an unexpected and troubling finding.”

 

To help slow the emergence of lethal superbugs, clinicians and pharmacologists will need to adopt new therapeutic tactics against persisters. “Our study offers compelling data that when treating bacterial populations, we have to get rid of the persisters,” said Brynildsen.

 

The conventional theory was that because many antibiotics only attack cellular targets involved in growth, persisters are often slow or nongrowing cells. Once the antibiotic threat has passed, persister cells then go back into growth mode, dividing into new bacterial daughter cells as usual. Therefore their descendants will not be more resistant than normal cells.

 

Besides beating ofloxacin, some persisters’ progeny showed resistance to antibiotics with completely different mechanisms of action, including the blocking of cell wall formation or the gumming up of other bio-molecules.

 

Brynildsen said, “Usually when an antibiotic is used, there is a concern that resistance to that specific drug would arise, ” “Accelerating resistance to other classes of antibiotics, as we saw in our study, is a much worse scenario because it even further limits your therapeutic options.”

Nathalie Balaban, a professor of physics at Hebrew University in Jerusalem, said that “the need to find combinations of treatments that are specifically aimed at reducing the persister populations, which would then reduce the probability to evolve resistance.”

Abstract
Persister bacteria travel an alternate path to antibiotic resistance

A persister bacterium is different from antibiotic-resistant bacteria. While most antibiotic-resistant bacteria have acquired genetic mutations that directly protect them against antibiotics, persisters do not possess such mutations. They have a better chance of survival than resistant mutants, because of certain genes they switch on or off before, during or after antibiotic therapy. It seems that the line between the antibiotic-resistant bacteria and persister bacteria is not as clear as scientists previously thought.  The researchers found that some persisters were more likely than standard bacteria to produce offspring with the direct, genetic-mutation resistance to antibiotics. The researchers found the persisters’ offspring went on to exhibit resistance not only to the drug their forbearers had survived but also to completely different classes of antibiotics.