Arbeitsgruppe Kretschmer
Dorothee Kretschmer
Interfakultäres Institut für Mikrobiologie und Infektionsmedizin
Auf der Morgenstelle 28
72076 Tübingen
Germany
Tel.: +49 (7071) 29-75937
E-Mail: dorothee.kretschmer@uni-tuebingen.de
Research Focus
1.The human innate system is equipped with multiple mechanisms to detect microbe-associated molecular patterns (MAMPs) to fight bacterial infections. Some of these MAMPs are sensed by G protein-coupled receptors (GPCRs) and lead to chemotactical leukocyte influx.
Formyl-peptide receptors (FPRs) belong to such GPCRs and recognize bacterial formylated peptides. We could demonstrate that staphylococcal Phenol-soluble modulin (PSM) peptides are chemoattractive to human phagocytes and are sensed by the human FPR2 receptor. How the activation of FPRs expressed by epithelia cells influence the outcome of infections and wound healing is part of our ongoing research.
2. A further group of MAMP sensing GPCRs are free-fatty acid receptors. The interaction between short-chain fatty acids (SCFA) and host cells has been primarily investigated in the intestinal lumen. In addition, members of the skin microbiome produce SCFAs, which are known ligands of the seven-transmembrane G-protein-coupled receptor free-fatty acid receptor (FFAR2). FFAR2 (previous GPR43) is expressed not only by enterocytes but also by neutrophils. Targeted activation of FFAR2 in neutrophils diminishes susceptibility towards infections by Staphylococcus aureus. How FFAR2 activation can be modulated and how bacteria circumvent FFAR2 activation is currently under investigation.
3. Bacteriophages are viruses of microbes which are important for bacterial population dynamics and promising antimicrobial agents for future clinical application. We focus on indentifying how bacteriophages bind and infect the important pathogens Staphylococcus aureus and Staphylococcus epidermidis via binding to the cell wall teichoic acid (WTA) glycosylation's. We are especially interested in the wall teichoic acid composition and the receptor binding proteins (RBPs) of staphylococci.
Ausgewählte Publikationen
1. Garrett SR, Mietrach N, Deme J, Bitzer A, Yang Y, Ulhuq FR, Kretschmer D, Heilbronner S, Smith TK, Lea SM, Palmer T. A type VII-secreted lipase toxin with reverse domain arrangement. Nat Commun. 2023;14(1):8438. doi: 10.1038/s41467-023-44221-y.
2. Slavetinsky J, Lehmann E, Slavetinsky C, Gritsch L, van Dalen R, Kretschmer D, Bleul L, Wolz C, Weidenmaier C, Peschel A. Wall Teichoic Acid Mediates Staphylococcus aureus Binding to Endothelial Cells via the Scavenger Receptor LOX-1. ACS Infect Dis. 2023;9(11):2133-2140. doi: 10.1021/acsinfecdis.3c00252.
3. Kengmo Tchoupa A, Kretschmer D, Schittek B, Peschel A. The epidermal lipid barrier in microbiome-skin interaction. Trends Microbiol. 2023;31(7):723-734. doi: 10.1016/j.tim.2023.01.009.
4. Lebtig M, Scheurer J, Muenkel M, Becker J, Bastounis E, Peschel A, Kretschmer D. Keratinocytes use FPR2 to detect Staphylococcus aureus and initiate antimicrobial skin defense. Front Immunol. 2023;14:1188555. doi: 10.3389/fimmu.2023.1188555.
5. Kengmo Tchoupa A, Kretschmer D, Schittek B, Peschel A. The epidermal lipid barrier in microbiome-skin interaction.Trends Microbiol. 2023 Feb Review.
6. Kretschmer D, Breitmeyer R, Gekeler C, Lebtig M, Schlatterer K, Nega M, et al. Staphylococcus aureus Depends on Eap Proteins for Preventing Degradation of Its Phenol-Soluble Modulin Toxins by Neutrophil Serine Proteases. Front Immunol. 2021;12:701093. doi: 10.3389/fimmu.2021.701093.
7. Schlatterer K, Beck C, Schoppmeier U, Peschel A, Kretschmer D. Acetate sensing by GPR43 alarms neutrophils and protects from severe sepsis. Commun Biol. 2021;4(1):928. doi: 10.1038/s42003-021-02427-0.
8. Weiss E, Schlatterer K, Beck C, Peschel A, Kretschmer D. Formyl-peptide receptor activation enhances phagocytosis of community-acquired methicillin-resistant Staphylococcus aureus. J Infect Dis. 2019. doi: 10.1093/infdis/jiz498.
9. Schlatterer K, Beck C, Hanzelmann D, Lebtig M, Fehrenbacher B, Schaller M, Ebner P, Nega M, Otto M, Kretschmer D, Peschel A. The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from Staphylococcus aureus. mBio. 2018;9(6). doi: 10.1128/mBio.01851-18.