Timing is key for bacteria surviving antibiotics
For bacteria facing a dose of antibiotics, timing might be the key to evading destruction. In a series of experiments, Princeton researchers found that cells that repaired DNA damaged by antibiotics before resuming growth had a much better chance of surviving treatment.
When antibiotics hit a population of bacteria, often a small fraction of "persister" cells survive to pose a threat of recurrent infection. Unlike bacteria with genetic resistance to antibiotics, evidence suggests that persisters stay alive in part by stalling cellular processes targeted by the drugs.
In a new study, Princeton researchers examined a class of antibiotics that target bacterial DNA. In bacterial populations, some cells repair damaged DNA before resuming growth, and others resume growth before making repairs.
The researchers found that those that make repairs before resuming growth generally are the ones that survive as persisters. The research advances a long-term goal to make antibiotic treatment more effective.
In results published June 18 in the Proceedings of the National Academy of Sciences, Wendy Mok, a post-doctoral researcher, and Mark Brynildsen, an associate professor of chemical and biological engineering, analyzed the responses of E. coli bacteria to treatment with ofloxacin, an antibiotic that causes DNA damage by blocking enzymes needed for DNA replication and RNA transcription. Their work built on previous results from Brynildsen's lab, which revealed that persisters to ofloxacin required DNA repair machinery to survive.
"But that doesn't guarantee that they're necessarily going to survive," said Mok. "We hypothesized that the timing of DNA repair and the resumption of growth-related activities like DNA synthesis could impact the survival of persisters after treatment."