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Turning the self-defence of bacteria on themselves

In a major new research project funded by the Carlsberg Foundation's Semper Ardens programme, a research group at the Department of Molecular Biology and Genetics, Aarhus University, who studies bacterial survival and defence mechanisms, will spend the next five years investigating how to turn bacteria's natural immune systems against themselves as a part of future antibiotic treatment strategies. The Carlsberg Foundation has awarded DKK 10 million to Professor Ditlev E. Brodersen for the research project.

The project leader, Professor Ditlev E. Brodersen, here flanked by laboratory technician Lan Bich Van (left) and postdoc Ragnhild Skjerning, has received DKK 10 million from the Carlsberg Foundation's Semper Arden programme, which supports innovative and ambitious research projects.
The project studies how specific defence mechanisms are able to kill individual bacterial cells. In the laboratory, an agar plate with different dilutions of E. coli bacterial cells is examined for the effect of one of the defense proteins.

Humanity is currently facing a huge health challenge with new viral and bacterial infectious diseases that are emerging faster than we can produce new treatments for them. And unless we discover new antibiotics soon, the WHO predicts that by the middle of the 21st century, we will see over 10 million annual deaths worldwide due to resistant microorganisms.

Analysis of the DNA sequences of thousands of bacteria has revealed that even the smallest microorganisms contain an advanced immune system that protects them against viral infection. CRISPR-Cas is a well-known example of such an immune system that enables bacteria to respond to infection by viruses they have previously encountered. This type of immune system is called adaptive and is similar to the antibodies that our bodies produce when we are exposed to infection, which also provide protection for a longer period of time.

However, in addition to an adaptive immune system, bacteria, like humans, harbour advanced forms of innate immunity that act as an additional safeguard if CRISPR-Cas fails. These systems specifically recognise viral infection and, in many cases, result in the killing of the individual bacterial cell to protect the colony from further attack. It is this type of immune system that the new project will explore, including whether it is possible to artificially activate such systems in pathogenic bacteria in order to kill them.

Senior postdoc Ragnhild Skjerning, who is centrally involved in the new project, says, "The project will give us a unique opportunity to increase our understanding of how bacteria defend themselves against viruses, also known as bacteriophages. The grant from Carlsberg is groundbreaking and will give us a great opportunity to set up a state-of-the-art microbiology laboratory where we can investigate bacterial defence mechanisms and develop experience with new model organisms and experiments."

Scientific leader of the project, Professor Ditlev E. Brodersen, continues, "The enormous number of bacterial genome sequences available enables us to discover new molecular immune systems with homology to a type of enzymes called kinases, which we will investigate using a wide range of techniques in microbiology, biochemistry and structural biology. The fusion of all this information will give us a deep understanding of the underlying molecular mechanisms, and the vision is that in the future this will help us to develop completely different types of antibiotics than the ones we see on the market today."

The project entitled "Understanding the role of bacterial self-targeting kinase toxins in phage defence" runs from 2024-2029 and is supported by the Carlsberg Foundation with DKK 9,995,081 under the Semper Ardens Accomplish programme.

More information: www.carlsbergfondet.dk/da/Forskningsaktiviteter/Bevillingsstatistik/Bevillingsoversigt/CF23_1461_Ditlev-Egeskov-Brodersen

For further information, please contact

Professor Ditlev Egeskov Brodersen
Department of Molecular Biology and Genetics
Aarhus University, Denmark
deb@mbg.au.dk - Mobile: + 45 21669001