Scientists engineer bacteria to cope in challenging environments

Researchers at the Universities of Bristol and Hamburg have engineered bacteria with internal stores of nutrients that they can access when needed to survive extreme environmental conditions. The findings, published in ACS Synthetic Biology, pave the way for more robust biotechnologies based on modified microbes.

Synthetic biology allows scientists to reshape organisms and harness their capabilities to find innovative solutions ranging from sustainable biomaterial production to advanced pathogen and disease detection.

Dr. Thomas Gorochowski, co-senior author and Royal Society Research Fellow at the Bristol School of Biological Sciences, said, "Most of the biological systems we have created so far are fragile and break easily when removed from the carefully controlled conditions of the laboratory. This makes them difficult to deploy and scale up."

To solve this problem, the team focused on the idea of building up protein stores in cells when conditions are good, and then breaking them down when conditions are difficult and additional nutrients are needed.

Klara Szydlo, first author and PhD student at the University of Hamburg, explains, "Cells need building blocks like amino acids to function and survive. We modified the bacteria to have a protected supply of these acids, which can then be broken down and released when nutrients become scarce in the environment. This allows the cells to continue to function in times of need and makes them more robust to the unexpected challenges they face."

To create such a system, the team modified bacteria to produce proteins that could not be used directly by the cell, but were recognized by molecular machines called proteases. When nutrients fluctuate in the environment, these proteases can then be called upon to release the amino acids that make up the protein pool. The released amino acids allowed the cells to continue growing, even if the environment lacked the necessary nutrients. The system acted like a biological battery that the cell could draw from in the event of a power outage.

Dr. Gorochowski added, "Developing such a system is difficult because there are many different aspects of the design to consider. How big should the protein pool be? How fast should it be broken down? For what types of environmental fluctuations would this approach work? We had a lot of questions and no easy way to evaluate the different options."

To get around this problem, the team built a mathematical model that allowed them to simulate many different scenarios and better understand where the system worked well and where it failed. It turned out that a careful balance was needed between the size of the protein pool, the rate at which it was broken down when needed, and the length of time nutrients were scarce. More importantly, the model also showed that if the right combination of these factors were present, the cell could be completely protected from environmental changes.

Professor Zoya Ignatova, co-senior author from the Institute of Biochemistry and Molecular Biology at the University of Hamburg, concluded, "We were able to demonstrate that careful management of key cellular resource pools is a valuable approach to engineering bacteria that must function in harsh environments. This capability will become increasingly important as we deploy our systems in complex real-world environments, and our work is helping to pave the way for more robust engineered cells that are capable of safe and predictable operation."