Certain structurally conserved bacterial molecules, (Microbe-Associated Molecular Patterns, MAMPs) are directly recognized by dedicated host receptors to activate defense mechanisms. 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 FPR2 and of FPR2 agonists or antagonists in innate immunity are currently analyzed.
Dorothee Kretschmer studied Biology and obtained her Diploma (2006) and PhD degree (2010) in Microbiology in Tübingen. 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)
- 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
DFG - Transregional Collaborative Research Center TR-SFB 34 -Pathophysiology of Staphylococci