Microbes with advanced storage technology: Scientists have equipped the bacteria with a genetic record function to gain insight into what is going on in the gut of mice. Sensory microbes recorded the activity of their own genes as they passed through the digestive system. This reflected their experiences of nutrient delivery or disease processes in the gut of rodents. Scientists say this concept could lead to the development of a non-invasive diagnostic procedure.
Whether it is a human, animal, plant or microbe – whether or not a living being faces specific challenges is reflected in the activity of specific genes in his body. A messenger RNA (mRNA) is formed, which forms the basis of genetic control of function in cells and the entire body. This relationship is already used to demonstrate biological processes. However, there is a drawback: mRNA is not stable – cells quickly break down these molecules again. However, under the guidance of Randall Platt of ETH Zurich, in recent years, scientists have developed an advanced molecular storage system that can record transcription events, at least in bacteria, and then share that data.
The recording function is based on the Crispr / Cas system. Naturally, bacteria can use them as a simple immune memory storing genetic information about pathogens: if bacteria are attacked by viruses, they can incorporate fragments of the viral genome into their own genome carriers known as Crispr matrices. In it, short fragments of DNA from pathogens are archived. Genetic fragments of various pathogens are separated by short, identical DNA sequences. The information contained in the Crispr matrices can then help the bacteria to defend themselves if they are re-attacked by a known pathogen.
Sophisticated recording function
To use this concept as a data logger, scientists manipulated the system so that the bacteria incorporated fragments of their own messenger RNA into the Crispr matrix instead of viral DNA fragments. An enzyme is activated that translates RNA information back into DNA information. These elements are then built into the Crispr arrays. The converted messenger RNA fragments thus store information about which genes were active in the bacteria. Scientists can then collect this data through sequencing.
Platt and his colleagues were currently investigating the possibility of using this method in medical diagnostics. They administered to mice a strain of the gut bacteria Escherichia coli equipped with a storage function. These microorganisms then passed through the digestive systems of the test animals. Scientists isolated bacterial DNA from stool samples and analyzed them. In this way, they were also able to reconstruct in detail the genetic information of the stored messenger RNA fragments.
Collection of microbiological data in the gut
In this way, as reported by scientists, they were actually able to capture information about the activity of bacterial genes that appeared while traveling through the digestive system. It also reflected some aspects of the environment. “With this new method, we can obtain information directly from the gut without having to disrupt its function,” says co-author Andrew Macpherson of Inselspital Bern. Specifically, the researchers were able to demonstrate, through experiments with mice that were fed differently, how the bacteria adapted their metabolism to an adequate nutrient supply. “Bacteria are very sensitive to environmental conditions and adapt their metabolism to changing conditions, such as food,” explains Macpherson.
Further experiments also showed that the system can provide information about what other bacteria the sensory microbes in the gut have come into contact with. The researchers were also able to identify signs of inflammatory reactions: when they administered sensory bacteria to mice with enteritis and healthy control animals, they were able to identify some differences in the RNA messaging profile of the storage system.
The results now form an important basis for the further development of the system for medical applications, the researchers say. For example, sensory bacteria can be used to diagnose certain inflammatory bowel diseases, determine malnutrition, or explain which diet is right for a patient. The researchers emphasize that safety issues must first be clarified before the instrumented microbes can be used in humans. They are currently working on changes to their sensory bacteria which mean they cannot survive outside of the gut. “Basically, there are ways to use living genetically modified microorganisms in medicine for diagnostic or therapeutic purposes, if certain conditions are met,” says Platt.
Source: Swiss Federal Institute of Technology Zurich (ETH Zurich), Specialist article: Science, doi: 10.1126 / science.abm6038