TY  - JOUR
A1  - Hanzelmann, Dennis
A1  - Joo, Hwang-Soo
A1  - Franz-Wachtel, Mirita
A1  - Hertlein, Tobias
A1  - Stevanovic, Stefan
A1  - Macek, Boris
A1  - Wolz, Christiane
A1  - Götz, Friedrich
A1  - Otto, Michael
A1  - Kretschmer, Dorothee
A1  - Peschel, Andreas
T1  - Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants
T2  - Nature Communications
N2  - Sepsis caused by Gram-positive bacterial pathogens is a major fatal disease but its molecular basis remains elusive. Toll-like receptor 2 (TLR2) has been implicated in the orchestration of inflammation and sepsis but its role appears to vary for different pathogen species and clones. Accordingly, Staphylococcus aureus clinical isolates differ substantially in their capacity to activate TLR2. Here we show that strong TLR2 stimulation depends on high-level production of phenol-soluble modulin (PSM) peptides in response to the global virulence activator Agr. PSMs are required for mobilizing lipoproteins, the TLR2 agonists, from the staphylococcal cytoplasmic membrane. Notably, the course of sepsis caused by PSM-deficient S. aureus is similar in wild-type and TLR2-deficient mice, but TLR2 is required for protection of mice against PSM-producing S. aureus. Thus, a crucial role of TLR2 depends on agonist release by bacterial surfactants. Modulation of this process may lead to new therapeutic strategies against Gram-positive infections.
KW  - Pathogens
KW  - Toll-like receptors
Y1  - 2016
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/16597
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-165975
VL  - 7
ER  -