The human immune system uses oxidative stress as one of its strategies to kill bacteria. How bacteria react at the molecular level to various environmental stress, such as oxidative stress, plays a significant role in their survival. In a recently published study in PNAS, researchers at Chalmers University of Technology have shown how the bacterium Bacillus subtilis alters its proteins to survive oxidative stress.
When bacteria enter the human body, the immune system responds with a series of actions. For instance, oxidizing conditions can be created locally, where so-called reactive oxygen species are found in the human cells. These oxygen species chemically react with – and can damage – bacterial proteins and DNA.
Bacteria's defense when encountering environmental changes, such as oxidative stress, is to form multicellular structures known as biofilms. To keep bacterial cells together in a biofilm, they produce and secrete exopolysaccharides, which are large, sticky molecules that form a protective matrix around the cells, enhancing the resistance to environmental stress.
Protein modification to cope with challenges
In bacteria, biofilm formation is controlled by several mechanisms, one of which involves tyrosine kinases − proteins that phosphorylate key enzymes in the synthesis and transport of exopolysaccharide.
"My group has been working on protein phosphorylation in bacteria for more than two decades, and our motivation is to understand how bacteria use this protein modification to cope with environmental challenges. In our new study, we show how a model bacterium, Bacillus subtilis, modifies its protein tyrosine phosphorylation to survive oxidative stress," says Ivan Mijakovic, professor of Systems and Synthetic Biology at Chalmers, and the research leader of the study.
Biofilms become more resistant
It all starts with the enzyme DefA, which is highly sensitive to reactive oxygen species and becomes inactivated when oxidized. This inactive form begins to interact with an important tyrosine kinase, PtkA, in Bacillus subtilis and inhibits it. As a result, PtkA's activity decreases, leading to a change in the exopolysaccharides that are produced. This makes the biofilms more physically robust and more resistant to oxidative stress.
"A detailed understanding of the molecular mechanism leading to the inhibition of protein tyrosine kinases is important. Such molecular mechanisms are usually evolutionarily conserved, and what we discovered in our model bacterium B. subtilis is likely to apply to many other bacteria, including pathogens," says Ivan Mijakovic.
Why is this research area important, and how can the results be further pursued?
"We presented this result at an international conference on post-translational modifications in bacteria, and many researchers working with pathogenic bacteria were interested. They will now investigate whether this mechanism exists in their pathogenic bacterial strains. Oxidative stress is a major factor in pathogenicity, and this could lead to new ways to combat infections. We, on the other hand, will continue to push the frontier of science in our B. subtilis model,” says Ivan Mijakovic.
More about the study
Contact
- Deputy Head Of Department, Life Sciences
- Researcher, Systems Biology, Life Sciences