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Scientists: Diarrheal pathogens check body temperature


Intestinal bacteria recognize their host by the body temperature
Bacteria perceive the ambient temperature with special RNA structures. In the past, it was extremely difficult to track them down in the cells. But now there is a new procedure.

Scientists decode all RNA structures of a diarrhea pathogen
Using modern high-throughput sequencing methods, researchers have decoded all the RNA structures of a diarrhea at once. They discovered a whole range of temperature-sensitive structures, so-called RNA thermometers. "So far, we have only ever found individual RNA thermometers after a lengthy search and laboriously examined them one by one," explained project manager Prof. Dr. Franz Narberhaus from the Ruhr University Bochum in a communication from the university. The Bochum scientists published their results together with colleagues from the Helmholtz Center for Infection Research in Braunschweig and the University of Leipzig in the journal "Proceedings of the National Academy of Sciences" ("PNAS").

Bacteria can only spread from a certain temperature
“Bacteria of the genus Yersinia trigger inflammation of the intestinal wall and severe diarrheal diseases in humans. The pathogen causing the plague also belongs to this genus, ”the experts at the Helmholtz Center write on their website. The scientists discovered various molecular switches in Yersinia pseudotuberculosis that change their three-dimensional structure at a temperature of 37 degrees Celsius. According to the researchers, the bacteria can only spread in the host and trigger a disease. The identified structures therefore offer points of attack for future drugs that block the temperature-dependent change and thus render the bacteria harmless.

Folded RNA as a thermometer
It has been known for years that certain intestinal bacteria, such as the Yersinia pseudotuberculosis examined here, recognize their warm-blooded host by body temperature. For this purpose, the bacteria use folded RNA structures that melt at a certain temperature and thereby reveal previously inaccessible gene sequences. According to the scientists, these can then be translated into proteins that control the course of the disease. In order to detect such cell thermometers, the research team used a combination of biochemical RNA structure mapping and high-throughput sequencing. In doing so, they simultaneously decoded the over 1,750 RNA structures contained in the bacterial cell. According to the information, the scientists carried out the experiment at three different temperatures and each received a snapshot of the RNA diversity.

The method can be used universally
"In this way, we were able to observe the dynamic changes in RNA structures when the temperature rose, for example, from 25 to 37 degrees Celsius," explained the doctoral student responsible for this project at the Bochum Chair for Microorganisms, Francesco Righetti. "The technology we use is complex," explained the Braunschweig researcher Dr. Aaron nut. "But it has huge potential for everyone who is interested in the biological function of RNA structures." It doesn't matter whether you work with bacteria, plants, animals or human cells. The method can be used universally.

Large number of temperature-dependent genes
"Our results show that a surprisingly large number of genes from the diarrhea Yersinia pseudotuberculosis react directly to the body temperature of the host," said Franz Narberhaus. For follow-up experiments, the experts selected 20 genes, 16 of which were actually temperature-dependent. These belong to different functional groups. For example, some are involved in the bacterium's response to oxidative stress. "It makes sense to initiate such processes immediately after the host is infected, in order to arm against the defense mechanisms in the human gastrointestinal tract," says Prof. Petra Dersch, infection biologist from Braunschweig. Current investigations are to show whether the newly identified RNA structures play a decisive role in the infection. In addition, the scientists want to clarify whether there are active substances that can prevent the melting of RNA thermometers. These could inhibit the infection process. (ad)

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