Findings from research into bacterial cells’ behavior done by scientists at Northwestern University and the University of Texas-Southwestern could have implications for how infections are treated. They found that bacterial cells can “remember” brief temporary changes to their bodies and immediate surroundings and pass those memories on to their offspring without altering their DNA. They believe that scientists could hack this feature to circumvent antibiotic resistance in bacteria for several generations. 

Full details of the finding were published in Science Advances in a paper titled, “Irreversibility in Bacterial Regulatory Networks.” According to the scientists, their work challenges assumptions of how some of the simplest organisms transmit and inherit physical traits. 

“A central assumption in bacterial biology is that heritable physical characteristics are determined primarily by DNA,” said Adilson Motter, PhD, a professor of physics, director of the Center for Network Dynamics at Northwestern, and the study’s senior author. “But, from the perspective of complex systems, we know that information also can be stored at the level of the network of regulatory relationships among genes. We wanted to explore whether there are characteristics transmitted from parents to offspring that are not encoded in DNA, but rather in the regulatory network itself.”

To answer their question, Motter and his team turned to the common bacterium Escherichia coli because its gene regulatory network has been studied and documented in detail. They then used a mathematical model of the network to simulate the temporary deactivation and reactivation of individual genes. “We found that temporary changes to gene regulation imprint lasting changes within the network that are passed on to the offspring,” Motter said. “In other words, the echoes of changes affecting their parents persist in the regulatory network while the DNA remains unchanged.”

Exactly how cells transmit the changes encoded in the regulatory network to future generations without DNA is still an open question. Motter and his colleagues speculate that reversible perturbations to the cells spark an irreversible chain reaction within the regulatory network meaning as one gene deactivates, it affects the gene next to it in the network. By the time the first gene is reactivated, the cascade has already been established because genes form self-sustaining circuits that resist outside influences once activated. 

The scientists are now trying to test their theories in laboratory experiments using CRISPR technology that temporarily deactivates genes. To be clear, other types of perturbations could cause a similar effect, Motter noted. For example, they could have changed the temperature of the cells’ environment or the availability of nutrients or pH.

“It’s a network phenomenon,” Motter, who is an expert in the dynamic behaviors of complex systems, said. “Genes interact with each other. If you perturb one gene, it affects others.” 

It is also possible that other organisms may have the necessary elements to exhibit nongenetic heritability since E. coli’s regulatory network is similar to or simpler than those found in other organisms.

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