Probiotic microbes have become effective chasses for engineering diagnostic and therapeutic technologies. One of the most commonly engineered probiotic strains is Escherichia coli Nissle 1917 (EcN). Engineered strains of EcN have been successfully used to diagnose and treat bacterial infections, cancers, gastrointestinal bleeding, inflammatory disorders, and obesity, in a variety of animal models.
Microbial biocontainment is an essential goal for engineering safe living therapeutics. However, the genetic stability of them is a challenge, including kill switches. These switchers are among the most difficult circuits to maintain due to the strong selection pressure they impart.
Tae Seok Moon, an associate professor of energy, environmental and chemical engineering at the McKelvey School of Engineering at Washington University in St. Louis is developing a genetically engineered kill switch that integrates into any genetically engineered microbe, causing it to self-destruct under specific conditions.
In the study the research team demonstrated that the strains of bacteria with a kill switch can be selectively and efficiently killed inside a murine gut.
The team is developing actuators that go against millions of years of evolution that have acted in favor of self-preservation, asking the microbe to self-destruct. So far Moon has developed several kill switches, one of them causes a microbe to self-destruct once the ambient environment around it reaches a certain temperature.
The research team is interested in developing genetically engineered microbes to eat plastic as a way of disposing of harmful waste. During their experiments, the team tested microbes using multiple kill switches, up to four in the microbial DNA, and out of billions of microbes, only one or none may survive.
The experiments were performed using a mice model, but Moon would like to build kill switches for microbes that will be used in soil, perhaps to kill pathogens that are deadly to crops, or even in the human gut to cure diseases.
Moon believes that these types of modified microbes could be used to solve different global problems.
Brandie Jefferson (2022, Feb 9). Moon develops targeted, reliable, long-lasting kill switch. Washington University in St. Lous, The Source, News room. Retrieved from:
Rottinghaus, A.G., Ferreiro, A., Fishbein, S.R.S. et al. Genetically stable CRISPR-based kill switches for engineered microbes. Nat Commun 13, 672 (2022). https://doi.org/10.1038/s41467-022-28163-5