KOPS - The Institutional Repository of the University of Konstanz

Competitive Live-Cell Profiling Strategy for Discovering Inhibitors of the Quinolone Biosynthesis of Pseudomonas aeruginosa

Competitive Live-Cell Profiling Strategy for Discovering Inhibitors of the Quinolone Biosynthesis of Pseudomonas aeruginosa

Cite This

Files in this item

Files Size Format View

There are no files associated with this item.

PROTHIWA, Michaela, Felix ENGLMAIER, Thomas BÖTTCHER, 2018. Competitive Live-Cell Profiling Strategy for Discovering Inhibitors of the Quinolone Biosynthesis of Pseudomonas aeruginosa. In: Journal of the American Chemical Society : JACS. 140(43), pp. 14019-14023. ISSN 0002-7863. eISSN 1520-5126. Available under: doi: 10.1021/jacs.8b07629

@article{Prothiwa2018-10-18Compe-43674, title={Competitive Live-Cell Profiling Strategy for Discovering Inhibitors of the Quinolone Biosynthesis of Pseudomonas aeruginosa}, year={2018}, doi={10.1021/jacs.8b07629}, number={43}, volume={140}, issn={0002-7863}, journal={Journal of the American Chemical Society : JACS}, pages={14019--14023}, author={Prothiwa, Michaela and Englmaier, Felix and Böttcher, Thomas} }

Englmaier, Felix Böttcher, Thomas 2018-10-18 Englmaier, Felix Prothiwa, Michaela Quinolones of the human pathogen Pseudomonas aeruginosa serve as antibacterial weapons and quorum sensing signals and coordinate the production of important virulence factors. A central enzyme for the biosynthesis of these quinolones is the synthetase PqsD. We developed an activity-based probe strategy that allows to screen for PqsD inhibitors in a cellular model system of live cells of Escherichia coli overexpressing PqsD. This strategy allowed us to determine IC<sub>50</sub> values for PqsD inhibition directly in live cells. Our most potent inhibitors were derived from the anthranilic acid core of the native substrate and resulted in single-digit micromolar IC<sub>50</sub> values. The effectiveness of our approach was ultimately demonstrated in P. aeruginosa by the complete shutdown of the production of quinolone quorum sensing signals and quinolone N-oxides and a considerable inhibition of the production of phenazine virulence factors. 2018-11-06T10:27:42Z 2018-11-06T10:27:42Z eng Prothiwa, Michaela Böttcher, Thomas Competitive Live-Cell Profiling Strategy for Discovering Inhibitors of the Quinolone Biosynthesis of Pseudomonas aeruginosa

This item appears in the following Collection(s)

Search KOPS


Browse

My Account