Identification of commensal bacteria-associated immune checkpoints as novel targets for immunotherapy against multidrug-resistant Staphylococcus epidermidis strains
Immunotherapy against multi-resistant germs
Our immune system is in balance with the body's own bacterial environment. These so-called commensal bacteria are also essential for the correct functioning of our skin and integrity. Under certain circumstances commensal bacteria can develop resistance against antibiotics and become pathogenic organisms, causing fulminant and almost uncontrollable infections. Therefore, it is of central importance to identify the so far unknown interactions between microorganisms immune system orchestrating tolerance and host defense. Based on the expected data we will be able to encrypt and modulate the immune response against pathogenic and commensal bacteria.
In order to realize the ambitious project, we will analyze the interaction between S. epidermidis strains and the host cells to understand both the colonization and transformation to pathogenic strains. This knowledge is essential for the development of future host-based therapies and prevention.
The IRIS team is well prepared for this. The Institute of Microbiology and Hygiene at the University of Regensburg (WP1; Team Gessner) is already a reference center that coordinates various standardization initiatives in the field of microbial analysis in Germany and in the EU. WP1 will perform all bacteria-associated sequence analyses that are crucial for the IRIS-project. Human immune cells will be analyzed after contact with S. epidermidis strains at the Department of Dermatology of the University of Erlangen-Nuremberg (WP2; team Dudziak). This is of central importance to validate data that will be generated with other experimental models.
The Regensburg Center for Interventional Immunology (WP3; RCI-team Feurer/Ritter) has a profound expertise in the fields of immunotolerance and pathogen-host interactions. In addition, various platforms of methods have been established at the RCI, which allows a high-level realization of the project. All three teams have developed extensive know-how in their respective fields of expertise in the analysis and integration of bioinformatics data. These include in particular single cell RNAseq, ATAC analysis and microbiome sequencing data.
The aim of IRIS is to understand why the immune system recognizes but tolerates commensal skin bacteria such as S. epidermidis and does not induce defense mechanisms. We intend to specifically break down this immunological tolerance in order to enable protective immunity responses against multi-resistant germs.
With the funded project, we expect to be able to make an important contribution to the development of promising therapeutic approaches, where the immune system is reprogrammed in order to combat multidrug resistant germs. This approach would have the potential benefit of avoiding the use of classical reserve antibiotics, which in turn can trigger resistance. Such an endogenous control of multi-resistant bacteria would play a significant role for the health system and the economy in Bavaria and would have global impact as well.
• PD Dr. med. Wilma Ziebuhr, Universität Würzburg, Institut für Molekulare Infektionsbiologie, Universität Würzburg. Emailadresse: firstname.lastname@example.org
• PD Dr. rer. nat. Knut Ohlsen, Universität Würzburg, Institut für Molekulare Infektionsbiologie, Universität Würzburg. Emailadresse: email@example.com
• Dr. Martin Fraunholz, Lehrstul für Mikrobiologie, Universität Würzburg. Emailadresse: firstname.lastname@example.org
Prof. Dr. Dr. André Gessner
Institute for Microbiology and Hygiene, University of Regensburg
Prof. Dr. Diana Dudziak
project manager and speaker of the research association
Department of Dermatology, Friedrich-Alexander University of Erlangen
Prof. Dr. Markus Feuerer
Regensburg Center for Interventional Immunology (RCI)