Scientists have developed bacteria that can detect colitis in mice.

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    In the intestines of mammals live trillions of microorganisms that somehow affect the health and the occurrence of diseases. Most of them are poorly studied by modern science, and not many technologies have been developed to study the processes occurring in the intestine.

    On the other hand, bacteria have formed genetically-encoded sensors for tens of thousands of years that recognize different types of particles. Therefore, genetically modified sensory bacteria have sufficient potential for studying the intestines and diagnosing intestinal diseases. Like electricians who design circuits of their wires and electronic components, biologists use genetic schemes to program single-cell creatures to perform complex information processing operations.

    Biologists from Rice Universitycreated intestinal bacteria capable of recognizing colitis — an inflammation of the colon — in mice. Further development can be used to study how intestinal bacteria interact with the human body at the molecular level. In addition, bacteria can be a kind of test for monitoring the condition and diseases of the intestines.

    In their previous work, they suggested that changes in the intestinal microbiota, genetic predisposition and other factors may in some way influence the onset and development of inflammatory bowel diseases - Crohn's disease and ulcerative colitis.

    Based on a number of other previous studies, scientists have concluded that the number of thiosulfate molecules can be increased during colitis. It was difficult for them to study this connection, because animals do not have tools for a reliable instrument for measuring thiosulfate. The first goal of the team of scientists was to develop such a tool.

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    Work on the project began in 2015, and his idea was to use sensory bacteria. In this case, we are talking about genetically modified E. coli ( Escherichia coli ), which, after modification, should determine the thiosulfate and the sulfur compounds associated with it. There is a connection between the metabolism of sulfur in the intestines and inflammation, and scientists knew that to diagnose inflammation of the colon, it was necessary to measure them.

    Researchers have managed to understand the programming methods of E. coli. The bacterium began to produce fluorescent green protein in response to specific stimuli. Until now, no other organism had known genes that would be used to determine thiosulfate. A small amount exists only for other compounds.

    Research co-author Ravi Shet in 2015 used a computer program to identify potential sensors for thiosulfate and other compounds in the Shewanella genome — such as bacteria that live in marine sediments. A group of scientists suggests that Shewanella probably breathes these molecules and uses sensors to turn on the appropriate enzymes in their presence.

    Biologists spent one year developing a modified E. coli bacterium to react to potential biomarkers, changing its color to green. It took another year to prove that the system works and actually detects inflammation of the colon in mice.

    Researchers forced to swallow two drops with a billion bacteria with sensors of both healthy mice and colitis mice. After six hours, scientists measured the activity of bacteria in each group. The control green protein could be detected using a flow cytometer .

    The team found that the thiosulfate sensor is activated in mice with inflammation and is not activated in healthy ones. In addition, it was found that the stronger the inflammation, the more active the sensors were. It is not yet known whether elevated thiosulfate levels can be a reliable indicator of human colitis, but sensory bacteria can be modified to respond to other compounds or molecules.

    In the future, researchers plan to develop a test for inflammation at home, which in case of illness will change the color of feces. Such a test will help reduce unnecessary and costly visits to the doctor and colonoscopy procedures. To achieve this goal, the team began collaborating with gastroenterologists from Baylor College of Medicine .

    Scientific work published in the journal Molecular Systems Biology April 3, 2017
    DOI: 10.15252 / msb.20167416

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