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
JF  - 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
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165975
VL  - 7
ER  - 
TY  - JOUR
A1  - Claus, Heike
A1  - Hubert, Kerstin
A1  - Becher, Dörte
A1  - Otto, Andreas
A1  - Pawlik, Marie-Christin
A1  - Lappann, Ines
A1  - Strobel, Lea
A1  - Vogel, Ulrich
A1  - Johswich, Kay
T1  - A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis
JF  - Scientific Reports
N2  - Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39% of disease isolates, but only in 3.4% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.
KW  - Meningitis
KW  - Pathogens
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200956
VL  - 9
ER  -