However, most of the known MAMPs are shared by commensals and pathogens and do not allow a discrimination between innocuous and aggressive bacteria. Using defined bacterial mutants we could demonstrate that staphylococcal PSM peptide leucocidins are chemoattractive to human phagocytes and are sensed by the human FPR2 receptor, which has hardly been implicated in innate immunity before. Hence, PSMs represent true pathogen-associated signals that attract leukocytes in relation to staphylococcal virulence. The role of GPCR agonists or antagonists in innate immunity are currently under investigation
In addition, we found that PSMs are necessary for mobilizing TLR2 ligands. Therefore, we analysed the mechanism of how PSM mediated the release of such lipopeptides from the bacterial surface. We demonstrated that PSM peptides promote the release of vesicles from the cytoplasmic membrane of S. aureus. Thus, a crucial role of TLR2 depends on agonist release by bacterial surfactants and reveal that they are responsible for inflammation via vesicle release. TLR2 and FPR2 may be attractive targets for future anti-inflammatory therapies. How bacterial derived vesicles influence infections, is part of our ongoing research.
Dorothee Kretschmer studied Biology and obtained her Diploma (2006) and PhD degree (2010) in Microbiology in Tübingen. During this time her son and daughter were born. After holding a postdoctoral position in the lab of Andreas Peschel in Tübingen she establishes her junior group since 2011 focusing on Staphylococcus aureus host/pathogen interaction with emphasis on the role of pathogen recognition receptors in Gram-positive infections.
- Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, Kennedy AD, Dorward DW, Klebanoff SJ, Peschel A, DeLeo FR, Otto M (2007) Identification of novel cytolytic peptides as key virulence determinants of community-associated MRSA. Nature Med 13:1510-4
- Kretschmer D, Gleske AK, Rautenberg M, Wang R, Köberle M, Bohn E, Schöneberg T, Rabiet MJ, Boulay F, Klebanoff SJ, van Kessel KP, van Strijp JA, Otto M, Peschel A (2010) Human formyl peptide receptor 2 (FPR2/ALX) senses highly pathogenic Staphylococcus aureus. Cell Host Microbe 7, 463-473.
- Kretschmer D, Nikola N, Dürr M, Otto M, Peschel A. The Virulence Regulator Agr Controls the Staphylococcal Capacity to Activate Human Neutrophils via the Formyl Peptide Receptor 2. J Innate Immun 4:201-12, 2012.
- Bloes DA, Otto M, Peschel A, Kretschmer D. Enterococcus faecium stimulates human neutrophils via the formyl-peptide receptor 2. PLoS One, 7:e39910, 2012.
- Cheung GY, Kretschmer D, Duong AC, Yeh AJ, Ho TV, Chen Y, Joo HS, Kreiswirth BN, Peschel A, Otto M. (2014). Production of an attenuated phenol-soluble modulin variant unique to the MRSA clonal complex 30 increases severity of bloodstream infection.PLoS Pathog. 10(8):e1004298
- Bloes D, Kretschmer D, Peschel A. (2015) Enemy attraction: bacterial agonists for leukocyte chemotaxis receptors, Nat Rev Microbio,13(2):95-104
- Kretschmer D, Rautenberg M, Linke D, Peschel A (2015) Peptide length and folding state govern the capacity of staphylococcal ß-type phenol-soluble modulins to activate human formyl-peptide receptors 1 or 2. J Leukocyte Biol, in press
- Hanzelmann D, Joo HS, Franz-Wachtel M, Hertlein T, Stevanovic S, Macek B, Wolz C, Götz F, Otto M, Kretschmer D*, Peschel A. Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants. Nat Commun. 2016 Jul 29;7:12304 (*, corresponding author)
- 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 Nov 20;9(6). pii: e01851-18.
- Weiss E, Hanzelmann D, Fehlhaber B, Klos A, von Loewenich FD, Liese J, Peschel A, Kretschmer D (2018) Formyl-peptide receptor 2 governs leukocyte influx in local Staphylococcus aureus infections. FASEB J. 2018 Jan;32 (1):26-36
- Formyl-peptide receptors in infection, inflammation and cancer. Weiß E, Kretschmer D.Trends Immunol. 2018 Oct;39(10):815-829. Review
- 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 Oct 1.