Researchers have analyzed what happens when a species of Yersinia switches into attack mode.

Yersinia pseudotuberculosis is transmitted via contaminated food. When it arrives in the intestine of the warm-blooded host, it secretes the cytotoxic necrotizing factor (CnfY) toxin, which triggers acute inflammatory reactions and increases the effect of other pathogenic substances.

Researchers at Ruhr-Universität Bochum (RUB) in Germany examined RNA thermometers, which signal to the bacteria whether they are in the host. With colleagues from the Helmholtz Institute for Infection Research in Braunschweig, they showed that bacteria with deactivated RNA thermometers can no longer trigger an infection. Findings were published in the journal Plos Pathogens.

RNA thermometers are responsible for temperature measurement. They are sections in the messenger RNA of many genes that contain the blueprint for disease-causing proteins.

“We knew from previous studies that Yersinia bacteria are very sensitive to temperature changes and recognize that they are in their host on the basis of body temperature,” said Professor Franz Narberhaus, the RUB chair of microbial biology.

Step towards stopping infection
At low temperatures, so outside the host, RNA thermometers prevent the RNA from being read and translated into proteins. After infection of the warm-blooded host, so at a temperature of around 37 degrees C (99 degrees F), the RNA structures melt. They can then be written into proteins that have a harmful effect on the host.

It could be possible to stop bacterial infection by preventing melting of RNA structures. However, scientists do not yet know of any substances that freeze RNA thermometers in the closed state.

Christian Twittenhoff used isolated cell components of the pathogen to show which structure the RNA thermometer for the CnfY toxin assumes and where it melts. The biologist created a model that documents how the thermometer opens. It also shows how the ribosome – the cell component on which the messenger RNA is translated into a protein – docks to the messenger RNA.

Researchers demonstrated the role of the RNA thermometer in the disease process. They infected mice with Yersinia bacteria that either had functioning RNA or inactivated RNA thermometers that could not melt at 37 degrees C (99 degrees F). The bacterial strains with modified RNA thermometers were not able to make mice ill.

Twittenhoff compared the gene of the CnfY toxin with toxin genes of other pathogens using bioinformatics. Findings suggest other toxin genes might also be regulated by RNA thermometers.

Investigating Salmonella and Campylobacter
Meanwhile, researchers at Julius-Maximilians-Universität (JMU) Würzburg will investigate different chemical stimuli and regulatory signaling pathways that control host adaptation of Salmonella and Campylobacter.

Pathogens are exposed to chemical stimuli and stress conditions during the infection process. They have various survival and adaptation strategies to deal with changing conditions. However, the molecular mechanism of how a given stimuli activates particular adaptation responses is mostly unknown.

The StressRegNet consortium is led by Professor Cynthia Sharma from the JMU Institute of Molecular Infection Biology/Research Center for Infectious Diseases (IMIB/ZINF) and junior research group leader Dr. Ana Rita Brochado from the ZINF/Biocenter with Professor Christian Müller from the Institute of Statistics at Ludwig-Maximilians-Universität Munich.

Using high-throughput automation technologies, the researchers aim to expose the two bacterial pathogens to a library of more than 3,000 different small molecules. The gene expression responses and stress reactions triggered by these chemical molecules will then be measured, with a focus on regulation by small regulatory RNA molecules.

This dataset will be investigated using machine learning techniques for specific signals and stress responses related to antibiotic sensitivity and host interactions.

The work should provide new insights into the regulatory networks of bacteria, which is essential for developing antimicrobial strategies. It is one of six projects part of the Bavarian research network bayresq.net which started in January 2020.

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