TY  - JOUR
A1  - Ashraf, Kerolos
A1  - Yasrebi, Kaveh
A1  - Hertlein, Tobias
A1  - Ohlsen, Knut
A1  - Lalk, Michael
A1  - Hilgeroth, Andreas
T1  - Novel effective small-molecule antibacterials against \(Enterococcus\) strains
JF  - Molecules
N2  - \(Enterococcus\) species cause increasing numbers of infections in hospitals. They contribute to the increasing mortality rates, mostly in patients with comorbidities, who suffer from severe diseases. \(Enterococcus\) resistances against most antibiotics have been described, including novel antibiotics. Therefore, there is an ongoing demand for novel types of antibiotics that may overcome bacterial resistances. We discovered a novel class of antibiotics resulting from a simple one-pot reaction of indole and \(o\)-phthaldialdehyde. Differently substituted indolyl benzocarbazoles were yielded. Both the indole substitution and the positioning at the molecular scaffold influence the antibacterial activity towards the various strains of \(Enterococcus\) species with the highest relevance to nosocomial infections. Structure-activity relationships are discussed, and the first lead compounds were identified as also being effective in the case of a vancomycin resistance.
KW  - medicine
KW  - antibacterial activity
KW  - synthesis
KW  - derivatives
KW  - structure-activity
KW  - lead structure
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172628
VL  - 22
IS  - 12
ER  - 
TY  - JOUR
A1  - Mielich-Süss, Benjamin
A1  - Wagner, Rabea M.
A1  - Mietrach, Nicole
A1  - Hertlein, Tobias
A1  - Marincola, Gabriella
A1  - Ohlsen, Knut
A1  - Geibel, Sebastian
A1  - Lopez, Daniel
T1  - Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus
JF  - PLoS Pathogens
N2  - Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM), a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS) as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of flotillin mediates intermolecular interactions of T7SS proteins. We tested several small molecules that interfere with flotillin scaffold activity, which perturbed T7SS activity in vitro and in vivo. Our results suggest that flotillin assists in the assembly of S. aureus membrane components that participate in infection and influences the infective potential of this pathogen.
KW  - flotillin
KW  - scaffold protein
KW  - Staphylococcus aureus
KW  - type VII secretion system
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170035
VL  - 13
IS  - 11
ER  -