Bacterial mRNA and Protein Levels Under Stress

A researcher works with bacteria in the lab at the Department of Molecular Biology
Photo Credit: Gabrielle Beans

Scientific Frontline: Extended "At a Glance" Summary: Bacterial mRNA and Protein Levels Under Stress

The Core Concept: A study demonstrating that in disease-causing bacteria, messenger RNA (mRNA) levels do not always accurately predict protein abundance, particularly under severe stress conditions.

Key Distinction/Mechanism: While mRNA carries genetic information for translation, protein levels are influenced by post-transcriptional processes; under stresses like osmotic shock, changes in cellular "plans" (mRNA) occur faster than the "execution" (protein synthesis).

Major Frameworks/Components:

• Comparison of three human pathogens: Salmonella enterica Typhimurium, Yersinia pseudotuberculosis, and Staphylococcus aureus.
• Exposure to ten infection-relevant stress conditions.
• Observation that conditions causing the most significant expression changes result in the lowest correlation between RNA and protein levels.

Branch of Science: Molecular Biology, Microbiology, Proteomics, and Genetics.

Future Application: Enhanced accuracy in modeling bacterial stress responses and a better understanding of how pathogens adapt during human infection, potentially leading to improved diagnostic or therapeutic strategies.

Why It Matters: It highlights the limitations of using RNA alone to monitor bacterial behavior, emphasizing the need to study proteins directly to fully understand cellular responses to challenging environments.

Sena Gizem Süer, Stress Response Modeling PhD student at the Department of Molecular Biology and IceLab, working with bacteria at her lab bench.
Photo Credit: Gabrielle Beans

Researchers at Umeå University have identified stress conditions in which RNA and protein levels diverge in disease-causing bacteria. Under osmotic stress, they traced this mismatch to reduced protein production, showing why RNA alone may not always reveal what is happening in the bacterial cell.

During infection, bacteria encounter rapidly changing and stressful environments inside the body. To understand how they adapt, researchers often measure messenger RNA (mRNA), which carries information from genes that can be translated into proteins. While mRNA levels are widely used to monitor bacterial responses, proteins carry out much of the work inside the cell and are influenced by processes that occur after RNA has been produced.

Scientists have long known that mRNA levels do not perfectly predict protein abundance. What has remained unclear is how that relationship changes under different stresses and across different bacterial pathogens.

In a new study published in the scientific journal PNAS, researchers compared three human pathogens: Salmonella enterica Typhimurium, Yersinia pseudotuberculosis, and Staphylococcus aureus. By exposing them to ten infection-relevant conditions, they investigated whether the relationship between mRNA and protein levels was species-specific or broadly shared.

Across all three species, mRNA and protein levels generally followed the same trends. However, stresses that triggered the largest changes in gene and protein expression also showed the weakest agreement between RNA and protein levels. In other words, under some of the most challenging conditions, RNA provided a less complete picture of what was happening inside the cell.

“When bacteria receive a sudden warning from their environment, they immediately start changing the messages inside the cell about what needs to happen next,” says Sena Gizem Süer, a PhD student at the Department of Molecular Biology and part of the Stress Response Modeling at IceLab research school at Umeå University, and shared first author of the study. “The cells can change their plans faster than they can build the things needed to carry them out.”

One stress condition stood out: osmotic stress, which occurs when changes in the concentration of dissolved substances around a cell disturb its water balance. Pathogens can encounter such environments in the body, for example, in the gut lumen. Genes responding specifically to osmotic stress showed a particularly weak match between mRNA and protein levels in all three bacterial species.

To investigate why, the researchers combined computational analyses with laboratory experiments. Their analyses pointed to altered translation—the process in which ribosomes read mRNA and build proteins—under osmotic stress.

The experiments confirmed that bacteria continued to translate mRNA into proteins during osmotic stress, but at significantly reduced levels in both Yersinia and Salmonella.

“This agreement between computational and experimental approaches strengthened our confidence in the findings,” says Jérôme Arnoux, an interdisciplinary postdoctoral fellow at the Integrated Science Lab (IceLab) and the Department of Molecular Biology, and shared first author.

Exactly why translation slows remains unclear. The researchers discuss several possible explanations, including changes affecting the cell envelope and the transport of molecules into the cell, but further studies will be needed to identify the underlying mechanism.

“Researchers often use mRNA as a proxy for what is happening at the protein level,” says Kemal Avican, a research fellow at the Department of Molecular Biology and senior author of the study. “Our results show that we need to better understand the uncertainty in that relationship, particularly when studying bacterial pathogens under stress and during infection.”

The researchers are now extending the work to additional stress conditions that resemble environments bacteria encounter during infection.

“The ultimate goal is to be able to predict bacterial protein levels during infection. That is something we cannot currently do using proteomics alone,” says Avican.

Interdisciplinary Collaboration: The movement between computation and experiment is reflected in the team behind the study. Five of the eight authors are connected to the interdisciplinary research environment IceLab (Integrated Science Lab), where Avican is a group leader, Süer is part of the Stress Response Modeling research school, and Arnoux is an interdisciplinary postdoctoral fellow. The collaboration also brought together Avican with IceLab affiliates and fellow SciLifeLab group leaders André Mateus, whose lab contributed the proteomics work, and Cemal Erdem, whose group developed MOBILE, a computational tool used in this study.

Published in journal: Proceedings of the National Academy of Sciences

Title: Bacterial stress responses lower mRNA–protein level correlations

Authors: Sena G. Süer, Jérôme Arnoux, Yi Y. Lim, Ganeshwari Dhurve, Rabia Şen, Cemal Erdem, André Mateus, and Kemal Avican

Source/Credit: Umeå University | Gabrielle Beans Picón

Edited by: Scientific Frontline

Reference Number: mbio092126_01

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