Researchers have previously built genetic circuits inside model organisms such as E. Coli. However, such strains are only found at low levels within the human gut, according to Timothy Lu, an associate professor of biological engineering, electrical engineering and computer science, who led the research alongside Christopher Voigt, a professor of biological engineering at MIT.
"We wanted to work with strains like Bacteroides thetaiotaomicron that are present in many people in abundant levels, and can stably colonise the gut for long periods of time," Lu said.
The team developed a series of genetic parts that can be used to precisely programme gene expression within the bacteria. "Using these parts, we built four sensors that can be encoded in the bacterium's DNA that respond to a signal to switch genes on and off inside B. thetaiotaomicron," Prof Voigt added.
To enable the bacteria to remember and report information externally, the researchers equipped B. thetaiotaomicron with used a class of proteins known as recombinases. These are claimed to record information into bacterial DNA by recognising specific DNA addresses and inverting their direction.
The researchers also implemented a technology known as CRISPR interference, which can be used to control which genes are turned on or off in the bacterium. The researchers used it to modulate the ability of B. thetaiotaomicron to consume a specific nutrient and to resist being killed by an antimicrobial molecule.
The researchers suggest that more advanced genetic computing circuits could be built upon this genetic toolkit in Bacteroides to enhance their performance as non-invasive diagnostics and therapeutics.
