Researchers unveil a series of sensors, memory switches, and circuits that can be encoded in the common human gut bacterium. These basic computing elements will allow the bacteria to sense, memorize, and respond to signals in the gut, with future applications that might include the early detection and treatment of inflammatory bowel disease or colon cancer.
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. “We wanted to work with strains like B thetaiotaomicron that are present in many people in abundant levels, and can stably colonize the gut for long periods of time,” Lu says.
METHOD: A series of genetic parts was made that can be used to precisely program gene expression within the bacteria. “Using these parts, we built 4 sensors that can be encoded in the bacterium’s DNA that respond to a signal to switch genes on and off inside B. thetaiotaomicron,” Voigt says. These can be food additives, including sugars, which allow the bacteria to be controlled by the food that is eaten by the host.
To sense/ report pathologies, incl bleeding or inflammation, the bacteria will need to remember this info and report it externally. So they equipped B. thetaiotaomicron with a form of genetic memory. They used recombinases, which can record information into bacterial DNA by recognizing specific DNA addresses and inverting their direction + they used CRISPR interference, which can be used to control which genes are turned on or off. The researchers used it to modulate ability of B. thetaiotaomicron to consume a specific nutrient and resist being killed by an antimicrobial.
The genetic tools and switches functioned within B. thetaiotaomicron colonizing the gut of mice. When the mice were fed food containing the right ingredients, they showed the bacteria could remember what the mice ate.
They now plan to expand the application of their tools to different species of Bacteroides as microbial makeup of the gut varies from person to person. The concept of using microbes to sense and respond to signs of disease could also be used elsewhere in the body, he adds. In addition, more advanced genetic computing circuits could be built upon this genetic toolkit in Bacteroides to enhance their performance as noninvasive diagnostics and therapeutics. “For example, we want to have high sensitivity and specificity when diagnosing disease with engineered bacteria,” Lu says. “To achieve this, we could engineer bacteria to detect multiple biomarkers, and only trigger a response when they are all present.” http://newsoffice.mit.edu/2015/basic-computing-for-bacteria-0709
The illustration depicts Bacteroides thetaiotaomicron (white) living on mammalian cells in the gut (large pink cells coated in microvilli) and being activated by exogenously added chemical signals (small green dots) to express specific genes, such as those encoding light-generating luciferase proteins (glowing bacteria).
Credit: Janet Iwasa
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