Microbes with advanced storage technology: Researchers have provided bacteria with a genetic recording function and thus gained insight into the processes in the gut of mice. The sensor microbes recorded their gene activity as they traveled through the digestive system. This reflected their experiences with nutrient supplies or disease processes in the rodents’ gut. The researchers say the concept could lead to the development of a non-invasive diagnostic procedure.
Whether it is a human, animal, plant or microbe – whether an organism faces certain challenges is reflected in the activity of certain genes in its body. Messenger RNA (mRNA) is formed, which forms the basis of genetic control of functions in cells and the entire organism. This relationship is already used to demonstrate biological processes. However, there is a drawback: mRNA is not stable – cells break down these molecules quickly again. However, researchers led by Randall Platt of ETH Zurich have developed a sophisticated molecular storage system in recent years that can record transcription events, at least in bacteria, and then make that data available.
The recording function is based on the Crispr/Cas system. Naturally, bacteria can use it as a simple immune memory that stores genetic information about pathogens: if bacteria are infected with viruses, they can incorporate parts of the viral genome into their own genome vectors, known as Crispr arrays. In it, short fragments of the DNA of pathogens are archived. Gene snippets of different pathogens are separated from each other by identical short DNA sequences. The information in Crispr arrays can help bacteria to defend themselves if they are attacked again by a known pathogen.
Duplicate recording function
In order to be able to use this concept as a data logger, the researchers manipulated the system in such a way that bacteria would incorporate extracts of their RNA into Crispr arrays rather than viral DNA fragments. The enzyme becomes active and translates the RNA information back into the DNA information. These pieces are then combined into the Crispr matrices. Thus, the transformed mRNA extracts store information about the genes that are active in the bacteria. The researchers can then collect this data sequentially.
Platt and colleagues have now explored the possibility of using this method in medical diagnosis. They administered a strain of the intestinal bacteria Escherichia coli equipped with a storage function to mice. These microbes then passed through the digestive tracts of the test animals. The researchers isolated bacterial DNA from stool samples and analyzed them. In this way, they were also able to specifically reconstruct the genetic information of the stored RNA extracts.
Microbial data collection in the gut
In this way, the scientists reported that they were already able to obtain information about the activity of genes in the bacteria that occurred during the journey through the digestive system. This also reflected certain aspects of the environment. “With the new method, we can get information directly from the gut without having to disrupt gut function,” says co-author Andrew Macpherson of Inselspital Bern. In concrete terms, the researchers were able to show, through experiments with mice that were fed differently, how the bacteria adapted their metabolism to their own nutrient supply. “Bacteria are very good at sensing environmental conditions and adapting their metabolism to changing conditions such as food,” MacPherson explains.
Other experiments have also shown that the system can provide information about other bacteria the sensor microbes have come into contact with in the gut. The researchers were also able to identify indicators of inflammatory reactions: when they administered the sensor bacteria to mice with gastroenteritis and healthy control animals, they were then able to identify some differences in the RNA profile of the storage system.
The scientists say the findings now form an important basis for further development of the system for use in medicine. For example, sensor bacteria can be used to diagnose certain inflammatory bowel diseases, to identify malnutrition, or to indicate an appropriate diet for a patient. The researchers point out that before processed microbes can be used in humans, safety issues must first be clarified. They are currently working on changes to their sensing bacteria which means they cannot survive outside of the intestine. “Essentially, there are ways to use genetically modified microorganisms as diagnostics or treatments in medicine, if certain conditions are met,” Platt says.
Source: Swiss Federal Institute of Technology in Zurich (ETH Zurich), specialized article: Science, doi: 10.1126 / science.abm6038
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