UM microbes on a double chain

The new self-destruct mechanism will not allow bacteria to scatter in the wrong place

Daria Zagorskaya, Vesti

Synthetic biology knows many ways to make microorganisms work for the benefit of humanity. Modified bacteria can recycle plastic waste, diagnose intestinal diseases, treat cancer, and even produce oxygen for the first colonizers of Mars.

However, there is one problem: no one knows what will happen if the microbes get out of control and slip away from their creators.

Previously, other scientists have already proposed a way by which bacteria could be killed on command, but in the case of escape, this option will not work. A separate difficulty is that microorganisms are able to mutate quickly, and researchers must be fully confident that the genes responsible for the elimination of violators will in any case be passed on to the next generation.

Now researchers from Harvard University, led by Pamela Silver, have developed a system of two molecular mechanisms that are "embedded" in the genome of microbes and automatically destroy them outside the "permitted zone". The model organisms were E. coli and a laboratory mouse, in whose body the modified bacteria were placed.

The first genetic switch does not allow microorganisms to remove a certain function from the genome during evolution. It consists of a gene encoding a deadly toxin for a bacterium, and a so-called "memory element" that suppresses the production of a toxic substance. If, as a result of the mutation, the memory element is cut out of the genome, the toxin content will grow, and the wrong cells will be destroyed.

The second mechanism operates on a similar principle, but in this case, the blocking of toxin production disappears at the moment when the ambient temperature drops from 37 to 22 degrees Celsius. Thus, such bacteria can exist only inside a living warm-blooded organism. But as soon as they leave its limits, for example, come out with feces, the ambient temperature will actually kill them.

Long-term observation of the lines of modified bacteria has shown that the mechanism of self-destruction persists for at least 140 generations. And after getting out of the mouse's body into the external environment, only one microorganism out of a hundred thousand survives.

Bacterial colonies – 4 concentrations, from minimum to maximum, at 37 (top) and 22 (bottom) degrees. A snapshot from the press release of the Wyss Institute Kill switches for engineered microbes gone rogue - VM.

"This breakthrough brings us much closer to the real use of synthetically engineered microorganisms in the human body or the environment," Silver says in a press release. "We are currently working on creating switch combinations that can respond to various environmental factors to ensure even tighter control."

To understand in detail the most complex system of restraining factors and molecular switches, you can read the article that was published by the authors of the work in the scientific publication Molecular Cell (Stirling et al., Rational Design of Evolutionarily Stable Microbial Kill Switches).

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